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389 publications mentioning hsa-mir-125a (showing top 100)

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-125a. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 347
In contrast, LIFR protein expression in miR-125a overexpressing MCF12A cells (Figure 2D) showed the opposite trend of decreased LIFR protein expression. [score:7]
The plasmids were then transfected into HEK293 cells to generate two cell lines with stable expression of 3′UTR-1 or 3′UTR-2. There was an inhibition of luciferase activity by 45% in 3′UTR-1 with ectopic expression of miR-125a. [score:7]
Overexpression or inhibition of miR-125a enhanced or suppressed stem cell expansion, respectively. [score:7]
A. Micrograph of primary breast cancer cells in culture B. & C. Flow cytometric analysis showing the decreased percentage of CSCs with inhibition of miR-125a D. Sphere forming assay demonstrating a decreased capacity of cells to form 3D spheres after inhibition of miR-125a E. analysis showing increased activity of LATS and TAZ in CSCs after inhibition of miR-125a. [score:6]
MiR-125a suppression could significantly control the CSC population and tumor suppression through LIFR, thus activating tumor suppression and the Hippo signaling pathway. [score:6]
Figure 6 A. Micrograph of primary breast cancer cells in culture B. & C. Flow cytometric analysis showing the decreased percentage of CSCs with inhibition of miR-125a D. Sphere forming assay demonstrating a decreased capacity of cells to form 3D spheres after inhibition of miR-125a E. analysis showing increased activity of LATS and TAZ in CSCs after inhibition of miR-125a. [score:6]
C. & D. analysis showing the expression of pSTAT3/STAT3 in MCF7 and MCF12A stem cells when challenged with miR-125a inhibitor and mimic respectively. [score:5]
Hippo signaling is a known tumor suppressor pathway [20- 21] and inhibition of miR-125a in CSCs leads to its activation. [score:5]
Effective miR-125a inhibition in MCF7 cells, and overexpression in MCF12A cells were achieved in 24 hrs (Figure 2A and 2B). [score:5]
In nonmalignant breast epithelial stem cells, overexpression of miR-125a inhibited the Hippo signaling pathway. [score:5]
However, LIFR protein was downregulated in both MCF7 and primary breast stem cells compared to MCF12A stem cells, thus demonstrating an inverse pattern of expression between miR-125a and LIFR (Figure 1E). [score:5]
Conversely, in the same study, an inverse expression of leukemia inhibitory factor receptor (LIFR) in relation to miR-125a was observed. [score:5]
In contrast, phosphorylation of LATS1 and TAZ was inhibited with miR-125a overexpression in MCF12A stem cells (Figure 4B). [score:5]
Our preliminary data suggests that JAK2-STAT3 signaling can be functioning downstream of Hippo signaling because the JAK2-STAT3 inhibition study demonstrated that the pTAZ levels in MCF7 stem cells are not affected, but inhibition of pTAZ levels by miR-125a negatively alters the pSTAT3 levels. [score:5]
Reduced expression of miR-125a in MCF7 cells dramatically increased LIFR protein expression (Figure 2C). [score:5]
I. Immunostaining of MCF12A spheres for SOX2 expression with over expression of miR-125a compared to mock controls. [score:4]
Cytoplasmic sequestration of TAZ could negatively affect the expression of stem cell self-renewal signaling networks, suggesting that miR-125a regulated the stem cell pool homeostasis by influencing the Hippo signaling pathway (Figure 5). [score:4]
These findings provided further evidence that miR-125a regulated the expression of LIFR. [score:4]
A. qRT-PCR data shows expression of miR-125a in MCF7 and human primary breast cancer cells (BC-052) compared to MCF12A cells B. Expression levels of miR-125a in MCF7 and primary breast CSCs as compared to MCF12A stem cells. [score:3]
We observed that miR-125a increased the phosphorylation of STAT3 in MCF12A derived stem cells and inhibition of miR-125a led to decreased phosphorylated STAT3 in MCF7 derived stem cells (Figure 7C and 7D). [score:3]
Similarly, in case of MCF12A-siLIFR, inhibition of miR-125a partially reduced the percentage of CD44 [+]/CD24 [−/low] cells (Figure 3J). [score:3]
B. qRT-PCR data shows effective over expression of miR-125a in MCF12A cells with miR-125a mimic. [score:3]
We also performed immunofluorescence for SOX2, a stemness protein marker in miR-125a overexpressing MCF12A spheres. [score:3]
Notably, miR-125a inhibition promoted the activation of Hippo signaling, with increased phosphorylation of LATS1 and TAZ (Figure 6E). [score:3]
F. Bar diagram depicting the phospho/total forms of STAT3 and TAZ corresponding to immunoblots in E. A. & B. analysis for MCF7 and MCF12A stem cells, demonstrating the influence of LIF and miR-125a inhibitor/mimic on TAZ. [score:3]
C. analysis for LIFR post miR-125a inhibition in MCF7 CSCs. [score:3]
Figure 7 A. & B. analysis for MCF7 and MCF12A stem cells, demonstrating the influence of LIF and miR-125a inhibitor/mimic on TAZ. [score:3]
Interestingly, in silico analysis revealed LIFR to be a putative target for miR-125a. [score:3]
In addition, the transcript levels of miR-125a in a cell population devoid of stem cells (ALDH-), in MCF12A and MCF7 cells, showed no difference in expression levels (Figure S2A). [score:3]
A. qRT-PCR data shows effective inhibition of miR-125a in MCF7 cells using 100nM of antagomirs. [score:3]
D. analysis for LIFR in miR-125a over expressing MCF12A stem cells. [score:3]
Figure 5 A. analysis in MCF7 stem cells showing the increased activity of LATS1 and TAZ after inhibition of miR-125a. [score:3]
We next determined the basal expression levels of miR-125a transcripts in stem cells obtained from MCF12A, MCF7, and primary breast cancer cells. [score:3]
In addition, we also provided evidence that miR-125a targeted LIFR, and as a result, influenced the activity of the Hippo signaling effector molecule TAZ. [score:3]
Interestingly, miR-125a promoted the expression of SOX2 (Figure 2I), which implied that miR-125a enhanced stemness in these cells. [score:3]
LIFR is a target of miR-125a. [score:3]
Stable clones of HEK293 expressing the 3′UTR or control sequences were plated at 60-70% confluency before they were transfected with 10 nM miR-125a mimic, using HiPerfect transfection reagent. [score:3]
The current study suggested that expression levels of miR-125a affects stem cell pool homeostasis in both malignant and nonmalignant conditions. [score:3]
Our data strongly suggested that miR-125a could be a potential therapeutic target against CSCs. [score:3]
MSY0000443) for miR-125a were used to modulate miR-125a expression. [score:3]
To achieve better treatment response and prognosis, miR-125a could potentially be a target for use with conventional chemotherapy against CSCs. [score:3]
Our findings provided a clear indication that the baseline expression levels of miR-125a in stem cells was different than in the normal cell population (Figure 1C). [score:3]
LIF is known to canonically activate STAT3, and LIFR inhibition by miR-125a appears to mimic the molecular phenomenon in this context. [score:3]
These findings prompted us to examine the role of miR-125a in malignant breast epithelial stem cells, and determine its influence on Hippo signaling by altering LIFR expression. [score:3]
In our previous studies of breast cancer occurrence, we found that miR-125a was upregulated in high risk breast epithelial stem cells compared to low risk groups [5]. [score:3]
An inverse trend was observed with inhibition of miR-125a in CSCs. [score:3]
We believe suppression of miR-125a in MCF7 stem cells is able to rescue the activation of Hippo signaling to some extent even in the presence of LIF. [score:3]
In this report, we identified LIFR as one of the targets for miR-125a. [score:3]
B. analysis in MCF12A stem cells showing the decreased activity of LATS1 and TAZ with over expression of miR-125a. [score:3]
Figure 1 A. qRT-PCR data shows expression of miR-125a in MCF7 and human primary breast cancer cells (BC-052) compared to MCF12A cells B. Expression levels of miR-125a in MCF7 and primary breast CSCs as compared to MCF12A stem cells. [score:3]
On the other hand, ectopic expression of miR-125a in LIF treated MCF12A stem cells inactivate Hippo signaling. [score:3]
Our findings demonstrated that miR-125a is tumor suppressor microRNA in bulk tumor cells of breast cancer origin, in agreement with previous studies [12- 14]. [score:3]
Inhibition of LIFR induced by miR-125a activated JAK2-STAT3 pathway stimulating a pro-carcinogenic molecular event in the non-malignant breast epithelial stem cells along with the inactivation of Hippo-TAZ signaling. [score:3]
Targeting miR-125a in primary breast cancer cells. [score:3]
E. Flow cytometric analysis shows increased percentage of stem cells with miR-125a over expression in MCF12A cells. [score:3]
These findings suggested that inhibition of miR-125a promoted phosphorylation of TAZ, resulting in its cytoplasmic sequestration. [score:3]
Inhibition in luciferase reporter activity was an indication that there was an existing functional association between miR-125a and LIFR. [score:3]
We also showed miR-125a modulation leads to alterations in LIFR expression in malignant and nonmalignant breast epithelial stem cells. [score:3]
Cancer stem cells express higher levels of miR-125a. [score:3]
Figure 4 A. analysis in MCF7 stem cells showing the increased activity of LATS1 and TAZ after inhibition of miR-125a. [score:3]
In this context, it appears that miR-125a activates STAT3 by inhibiting Hippo signaling. [score:3]
G. Flow cytometric analysis shows decreased percentage of stem cells with miR-125a inhibition in MCF7 cells. [score:3]
Overall, the results suggested that miR-125a regulates stem cell pool homeostasis by regulating LIFR. [score:3]
However, miR-125a is a cancer promoting microRNA in breast epithelial stem cells, unlike its action as a tumor suppressor in breast cancer cells. [score:3]
But addition of LIF in miR-125a suppressed MCF7 stem cells, actually rescues the activation of Hippo signaling to some extent. [score:3]
Transcript levels of miR-125a in human breast cancer tissues were found to be downregulated compared to normal breast tissues by 1.75 fold (Figure S1A). [score:3]
J. Inhibition of miR-125a abolishes the effect of LIFR silencing by reducing the percentage of CD44 [+]/CD24 [−/low] cells. [score:3]
I. miR-125a overrides the effects of LIFR over expression in MCF7 cells as evident by the increased percentage of CD44 [+]/CD24 [−/low] cells. [score:3]
We found that miR-125a inhibition in MCF7 stem cells led to activation of Hippo signaling. [score:3]
This was comparable to the effect of miR-125a overexpression on MCF12A cells. [score:3]
Figure 2 A. qRT-PCR data shows effective inhibition of miR-125a in MCF7 cells using 100nM of antagomirs. [score:3]
Simultaneously, stable clones of HEK293 expressing the control plasmid were transfected with the miR-125a mimic. [score:3]
miR-125a binding site on LIFR 3′UTR was obtained using TargetScan online portal. [score:3]
MiR-125a suppression activated Hippo signaling in CSCs. [score:2]
The expression of miR-125a in CSCs (ALDH+) derived from human primary breast cancer cells were compared to non-stem cells. [score:2]
Addition of LIF in combination with miR-125a inhibitor in MCF7 stem cells increased the levels of phosphorylated TAZ but didn't alter the levels of LIFR as compared to the LIF only group. [score:2]
Phosphorylation of LATS1 (T1079), and TAZ (Ser89) in miR-125a inhibited MCF7 stem cells was increased compared to mock control (Figure 4A). [score:2]
We found that miR-125a regulated stem cell pool homeostasis. [score:2]
E. & F. Immunostaining for TAZ in MCF12A stem cells demonstrates nuclear localization of TAZ with over expression of miR-125a compared to mock control. [score:2]
H. Sphere forming assay demonstrates lower percentage of 3D sphere forming cells in miR-125a inhibited MCF7 cells. [score:2]
Diagram represents a proposed mo del of miR-125a regulation of TAZ through LIFR leading to changes in the stem cell pool homeostasis. [score:2]
Cytoplasmic sequestration of TAZ in miR-125a inhibited MCF7 stem cells compared to mock control cells (Figure 4C and 4D) was observed. [score:2]
C. & D. Immunostaining for TAZ in MCF7 stem cells demonstrates sequestration of TAZ in the cytoplasm compared to mock control after miR-125a inhibition. [score:2]
MiR-125a suppression in primary breast cancer cells led to reduction in CSC traits. [score:2]
In this study, we examined the role of miR-125a in the regulation of malignant (CSC) and nonmalignant breast epithelial stem cells. [score:2]
In addition, miR-125a inhibition also led to a decrease in sphere formation by 19.83% in MCF7 cells, compared to mock control cells (Figure 2H). [score:2]
The results indicated an increase in the expression of miR-125a in CSCs by approximately 9 fold when compared to non-stem cancer cells (Figure S4A). [score:2]
Percentage of stem cells was observed to be increased by 22.15% with miR-125a overexpression in MCF12A cells, when compared to mock treated control cells (Figure 2E). [score:2]
Effect of miR-125a on JAK2-STAT3 regulation by LIF-LIFR interaction. [score:2]
Suppression of miR-125a in these CSCs led to a decrease in the CD44 [+]/CD24 [−/low] cell population by 20.60% compared to mock treated control cells in both cell lines (Figure 6B, 6C, and Figure S4B, C). [score:2]
Luciferase assay data for HEK293 cells demonstrating a decrease in the luciferase activity with addition of miR-125a mimics to wtLIFR 3′UTR-1 expressing cells but not in wtLIFR 3′UTR-2 and mutLIFR 3′UTR. [score:2]
Further, our findings reveal positive regulation of JAK2-STAT3 signaling by miR-125a. [score:2]
We hypothesized that miR-125a regulated breast epithelial stem cells through the Hippo signaling pathway mediated by LIFR. [score:2]
F. Sphere forming assay demonstrates higher percentage of 3D sphere forming cells in miR-125a over expressing MCF12A. [score:2]
However, miR-125a inhibition in MCF7 cells led to a decreased percentage (30.15%) of stem cells compared to mock control cells (Figure 2G). [score:2]
Together, the results indicated that LIFR was regulated by miR-125a. [score:2]
We next determined if the regulatory effects of miR-125a were mediated through LIFR. [score:2]
Overall, these findings suggested a regulatory role for miR-125a in nonmalignant and malignant breast epithelial stem cells. [score:2]
LIFR modulation mimics the effects of miR-125a. [score:1]
MiR-125a regulates stem cell pool dynamics. [score:1]
These findings suggested an inverse correlation between miR-125a and LIFR in stem cell populations, but not in the bulk cell population. [score:1]
MiR-125a regulated breast epithelial stem cells through Hippo signaling downstream of LIFR. [score:1]
To assess the impact of miR-125a and LIFR interactions on stem cell populations, MCF12A cells were treated with the miR-125a mimics and MCF7 cells were treated with the miR-125a antagomirs. [score:1]
Inverse correlation between miR-125a and LIFR in stem cells. [score:1]
MiR-125a overexpressing MCF12A cells showed an increased nuclear localization of TAZ compared to mock control cells (Figure 4E and 4F). [score:1]
Influence of miR-125a on JAK2-STAT3 signaling pathway. [score:1]
miR-125a impacts activity of Hippo signaling pathway through LIFR. [score:1]
Addition of LIF in combination with miR-125a mimics in MCF12A stem cells decreased the levels of phosphorylated TAZ along with LIFR. [score:1]
Effect of LIF on the action of miR-125a. [score:1]
Overall, our findings strongly suggested that miR-125a is important for the proliferative fate of both malignant and nonmalignant breast epithelial stem cells, therefore further affecting various stages of carcinogenesis. [score:1]
One hundred nM and 10 nM of the miR-125a antagomirs and mimics were used for MCF7 and MCF12A, respectively. [score:1]
Increase in miR-125a significantly decreased LIFR in nonmalignant epithelial stem cells. [score:1]
The miR-125a acts upstream of LIFR, thereby influencing the Hippo signaling pathway, downstream pro-proliferative and stem cell self-renewal genes, and finally the stem cell pool. [score:1]
Our aim was to validate the findings obtained from miR-125a modulated malignant and non-malignant breast epithelial cell lines. [score:1]
To further validate the effect of miR-125a on stem cell pool homeostasis, we used miR-125a mimics in MCF7-LIFR cells and checked for the percentage of CD44 [+]/CD24 [−/low] cells. [score:1]
MCF12A, MCF7, BC-051, and BC-052 cells were cultured to 70-80% confluency and treated with miR-125a mimics/antagomirs. [score:1]
LIFR modulation mimicked the effects of miR-125a on breast epithelial stem cells. [score:1]
Based on these data, it was clear that miR-125a was capable of influencing the CSC population in primary breast cancer tissues. [score:1]
Moreover, our findings provided evidence for altered subcellular localization of TAZ, after miR-125a modulation, which can be linked to activation/inactivation of Hippo signaling. [score:1]
This data demonstrates that addition of LIF along with miR-125a has an additive effect for inactivation of Hippo signaling in MCF12A stem cells. [score:1]
We further demonstrated that miR-125a influenced the Hippo signaling pathway through LIFR. [score:1]
We also showed that LIFR modulation replicated the effects of miR-125a on the stem cell pool. [score:1]
However, inverse relationship between miR-125a and LIFR were observed in other breast cancer cell lines also (Figure S3A & S3B). [score:1]
One hundred nM of the miR-125a antagomirs were also used for primary breast cancer cells. [score:1]
Figure 5 Our aim was to validate the findings obtained from miR-125a modulated malignant and non-malignant breast epithelial cell lines. [score:1]
As we show that miR-125a acts through LIFR, it was imperative to understand the role of its ligand LIF on the functioning of Hippo signaling (Figure 7A and 7B). [score:1]
With the aim to determine the basal levels of miR-125a in cancer and normal breast epithelial cells, we used malignant MCF7, primary breast cancer (BC052 and BC051) and non-malignant MCF12A cells. [score:1]
miR-125a modulation affects malignant and non-malignant breast epithelial stem cells. [score:1]
We analyzed the phosphorylation status of key proteins involved in Hippo signaling, along with subcellular localization of TAZ after miR-125a modulation in breast epithelial stem cells. [score:1]
Changes in CD44 [+]/CD24 [−/low] stem cell populations at 24 hrs after miR-125a modulation were then determined. [score:1]
This suggested that miR-125a played a different role in stem cells than in the bulk cell population. [score:1]
To further validate the proposed mechanism of miR-125a action on CSCs, immunoblotting for key proteins of Hippo signaling was performed. [score:1]
These findings were in agreement with previous reports regarding the role of miR-125a in stem cells of hematopoietic malignancies [15, 16]. [score:1]
H. Predicted interaction of miR-125a with LIFR in silico. [score:1]
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[+] score: 242
Other miRNAs from this paper: hsa-mir-125b-1, hsa-mir-125b-2
However, thus far, most of the studies on autoimmune diseases mainly focus on the expression pattern of miR-125, the targets and inflammatory pathway in this disease still need to be declared It has been uncovered that miRNAs are tightly associated with immune system by controlling the destiny of immune cells [56, 57], regulating the expression of target encoding genes, responding to stimulatory cues, and enhancing the response of immune cells to potential antigen as well as playing a key role in fate of immune cells. [score:14]
Up-regulated miR-125a significantly inhibits the malignant phenotypes by repressing the expression of matrix metalloproteinase 11 (MMP11) and vascular endothelial growth factor A (VEGF-A) both in vitro and in vivo [12], while the direct targets of miR-125b in miRNA -induced inhibition of hepatocellular carcinoma cell proliferation are Mcl-1 and IL6R [25]. [score:13]
The reviews above have shown that expression level of miR-125 family is distinguished in various types of disease, implying that the miR-125 could predict disease onset and might potentially serve as prognostic marker in disease-derived tissues and possibly in serum. [score:9]
Aberrant expression of miR-125 leads to up-regulation of Bcl-2, Mcl-1 et al. and down-regulation of Bak-1, TP53INP1 et al. and consequently to protect cells from apoptosis, which in turn promotes tumorigenesis. [score:9]
For instance, miR-125a has been identified down-regulated in systemic lupus erythematosus (SLE), and negatively regulated expression of the inflammatory chemokine RANTES, which is highly expressed in SLE samples and plays a key role in inflammatory progress [49]. [score:9]
In breast cancer, miR-125a and miR-125b were reported down-regulated in biopsy specimens and as tumor suppressors [23, 29, 30] by mediating the ERBB2 and ERBB3 pathway [22] or by targeting the ETS1 gene [31]. [score:8]
In certain contexts, miR-125 can down-regulate target oncogene as a tumor suppressor, reducing tumor proliferation and metastasis. [score:8]
We mainly focus on following four aspects: (1) the regulation of miR-125 at post-transcription level, (2) the function of miR-125 as tumor-suppressive or tumor-promoting properties, (3) potential acting of miR-125 as biomarker, and its possibility to be used as a therapeutic target in disease therapy, and (4) the immune-modulating functions of miR-125 and the involvement of this miRNA in immune responses to pathogen infections. [score:8]
Current progression also revealed a number of the miR-125 family target genes and their regulation pathways, which could supply the feasibility of using miR-125 as a therapeutic strategy to suppress diseases. [score:8]
In addition, in accordance with either disease-suppressive or - promoting properties of miRNAs in different diseases, miR-125’s ability as therapeutic agents has been delineated by many research groups. [score:7]
The down regulated miR-125 caused breast cancer but the up regulated miR-125 induced chemoresistance, and higher expression of miR-125 promoted ALL or AML nevertheless reduced expression of miR-125b resulted in metabolic pathways transformed in CLL. [score:7]
The aberrant expression of miR-125 was also found in different diseases other than cancers, such as autoimmune diseases [48]. [score:7]
As mentioned above, miR-125 family may contribute to the initiation and progression of diseases by acting as either suppressors or promoters in a number of cancers and other diseases [16, 17, 22, 23, 25, 28, 29], re-introduction of synthetic miR-125 or its antisense at specific sites could become a possible treatment option. [score:7]
Moreover, miR-125 influences the fate of immune cells by targeting and regulating a set of target genes to enhance the effect against intra- or extracellular pathogens, or responding to the regulation of specific signal stimulation like IL and IFN. [score:7]
In conclusion, miR-125 family plays crucial roles in immune system development and immunological host defense, including regulating differentiation of immune cells, responding to stimulatory cues in many different signal pathways involved in immune system, controlling expression of target genes, products of which partake in immune reactions as well as in immune responses to bacterial infection and to viral infection. [score:7]
Since aberrant expression of miRNAs exist in almost all types of cancers and several other diseases, the potential use of miR-125 as potent prognostic markers for early diagnosis of malignancies and other diseases has drawn more and more attentions. [score:7]
Subsequently miR-125a was shown to interfere with the viral translation, down -regulating the expression of the surface antigen [62]. [score:6]
Wang et al. reported that miR-125a, activated by EGFR, functions as a metastatic suppressor in lung cancer cells, inhibiting tumor formation and tube formation [28]. [score:5]
Ectopic expression of both miR-125a [12] and miR-125b [25] can inhibit the proliferation and metastasis of hepatocellular carcinoma. [score:5]
As summarized in Figure 1, the targets of miR-125 family are involved in different types of diseases pathogenesis. [score:5]
miR-125a also enhances invasive potential in urothelial carcinomas [39] and is up-regulated in basal cell carcinoma compared with adjacent nonlesional skin [40], while miR-125b suppresses Bmf -dependent apoptosis in human glioblastoma multiforme cells [41]. [score:5]
Moreover, Hong and colleagues have uncovered that the expression levels of miR-125b were much lower in HCC tissues than in non-tumor liver tissues [25], indicating that both miR-125a and miR-125b have low expression level and are inversely correlated with aggressiveness and poor prognosis in HCC, and could serve as the bio-marker for HCC diagnosis and prognosis. [score:5]
Experimentally, miR-125 -induced down-regulation of ERBB2 and ERBB3 has been uncovered to reduce cell motility and invasiveness of numerous cancers, including breast cancer [22] and endometrial cancer [72]. [score:4]
The regulatory network of miR-125 family in disease pathogenesis. [score:4]
Anti-apoptotic members of Bcl-2 family such as Bcl-w [65], Bcl-2 [66], Mcl-1 [65, 67], and Bak-1 [11, 44, 68, 69] acting as the Bcl-2 homologous antagonist, and others involved in apoptosis like P53 [69], TP53INP1 [11, 18], TNFAIP3 [70], p38α [71] et al., have all been demonstrated to be direct targets of miR-125 in previous studies. [score:4]
In contrast to the tumor-suppressive properties mentioned above, the members of miR-125 family, especially miR-125b, also act as oncogene in several cancers. [score:3]
MiR-125a was also reported to be significantly up-regulated in macrophases following oxidized low density lipoprotein (oxLDL) [50], inducing the formation of ischemic stroke [51]. [score:3]
As previous reported, miR-125 family plays an important role in normal cell homeostasis, cell metastasis and different diseases. [score:3]
It is noteworthy that the functions of miR-125 are controversial in different types of diseases. [score:3]
Members of Bcl-2 family and ones else involved in apoptosis are an important group of miR-125 targets. [score:3]
The different members of miR-125 family have been reported controversial properties in different types of cancer; they may contribute to the initiation and progression of cancers by acting as either tumor suppressors or oncogenes [15- 18]. [score:3]
ERBB2, which enhances kinase -mediated activation of downstream signaling pathways such as MAPK, has been verified to be the target for both miR-125a and miR-125b [22]. [score:3]
The theme of the present paper, however, is to summarize the function of miR-125 family in different contexts, particularly in disease condition. [score:3]
Among the most important miRNA families, miR-125 family has been reported to be implicated in a variety of carcinomas and other diseases as either repressors or promoters. [score:3]
Furthermore, an increasing number of studies have identified the target genes of miR-125 family in different cellular contexts, which highlights the precise properties of this miRNA in cellular pathways and networks, especially associated with carcinoma. [score:3]
Evidences deriving from the increasing number of papers showed that members of miR-125 family play a crucial role in diverse cellular processes and many diseases especially carcinomas. [score:3]
All together suggest that miR-125 plays important roles in autoimmune diseases. [score:3]
The advances that miR-125 and other miRNAs can be used in clinical applications exactly hold potential for future treatment of diseases. [score:3]
Potential of miR-125 for disease diagnosis and therapy. [score:3]
Among other targets of miR-125 associated with proliferation, metastasis and migration, HuR [73], Rock-1 [74], PDPN [75], STAT3 [27] and STARD13 [38] are five important genes identified, which can induce cell metastasis and migration, and in turn enhance tumorigenesis. [score:3]
The functional link of the miR-125 family in autoimmune diseases. [score:3]
MiR-125a interacted with the viral sequence and markedly suppressed the reporter activity. [score:2]
MiR-125 plays important roles in mitochondrial apoptosis pathway by targeting pro-apoptosis or anti-apoptosis gene depends on the cell context. [score:2]
MiR-125 has been shown its tumor-suppressor functions in several cancers including ovarian cancer [16, 19], bladder cancer [20], breast cancer [21- 23], hepatocellular carcinoma [12, 24, 25], melanoma [26], cutaneous squamous cell carcinoma [13] and osteosarcoma [27]. [score:2]
MiR-125 can act as cancer promoter or cancer repressor depends on the cell context, among which, the mitochondrial apoptosis pathway is the well illustrated role of miR-125 with the two faces (as shown in Figure 2). [score:1]
MiR-125 family is composed of three homologs hsa-miR-125a, hsa-miR-125b-1 and hsa-miR-125-2. MiR-125a has been found to be located at 19q13, while miR-125b is verified to be transcribed from two loci located on chromosomes 11q23(hsa-miR-125b-1) and 21q21(hsa-miR-125b-2) [6]. [score:1]
Further research is needed before miR-125 and other miRNAs can be used in clinical applications. [score:1]
Another important function of miR-125 is in immune responses to bacterial infection, and even shows to partake in damage accompanied by pathogenic bacteria. [score:1]
Involvement of the miR-125 family in solid tumors. [score:1]
MiR-125 involved in immune system development and immunological host defense. [score:1]
Vice versa, a variety of studies have exhibited tumor-promoting functions of miR-125 as a tumor promoter. [score:1]
Properties of the miR-125 family in hematological malignancies. [score:1]
Research on miR-125 in leukemia and breast cancer mo del may provide a new insight into current miRNA research. [score:1]
Taken together, miR-125 family has great perspective as a diagnostic and prognostic biomarker. [score:1]
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3
[+] score: 235
Other miRNAs from this paper: hsa-mir-125b-1, hsa-mir-138-2, hsa-mir-125b-2, hsa-mir-138-1
Since MBP is not present in the list of miR-125a-3p putative targets obtained from MyMIR, we reasoned that miR-125a-3p inhibitory effect is likely exerted on upstream players in the pathway culminating with OPC maturation and MBP expression. [score:7]
Globally these findings show that the biological role of miR-125a-3p changes depending on the developmental stage, and that, from embryonic life to adulthood, its expression moves from brain ventricles to parenchyma up to neurons of the cerebral cortex, where it is likely to repress the expression of non-neuronal genes. [score:6]
To confirm this hypothesis, we performed quantitative real time PCR experiments after miR-125a-3p over -expression in OPCs, and found that the expected reduction of Mbp mRNA was also accompanied by considerable downregulation of both Fyn, Nrg1 and Map1b (Fig. 4b). [score:6]
In line with the hypothesis of the modulation of early targets, during in vitro OPC differentiation miR-125a-3p is progressively up-regulated (Fig. 2e). [score:6]
These data show that when miR-125a-3p levels are high, oligodendrocyte maturation is blocked, and this could explain the high expression levels found during embryogenesis, to suggest that miR-125a-3p may, at the same time, promote neural specification and prevent the untimely expression of genes necessary for oligodendrocyte commitment/maturation and the subsequent myelination process that, indeed does not take place at this stage. [score:5]
Interestingly, by means of in situ hybridization, we found that miR-125a-3p is expressed throughout post-natal age in Olig2 [+] oligodendrocytes, suggesting that, in these cells, it is necessary for silencing SMAD4, in order to promote the expression of these genes and subsequent oligodendroglial specification. [score:5]
In postnatal brain, the expression of miR-125a-3p is restricted to neurons, both in cortex and striatum, and oligodendrocytes (Fig. 2c), whereas only a few cells also expressed GFAP and no apparent co-localization was found with microglia. [score:5]
This is in line with previous literature data demonstrating that miR-125a directly binds Smad4, a key regulator of pluripotent stem cell lineage commitment, thus potentiating early neural specification 9. Moreover, during postnatal life, SMAD4 and its cascade inhibit oligodendrogenesis by inducing the Id and Hes genes and by repressing Olig1 and Olig2 31. [score:5]
Thus, it is not surprising that miR-125a-3p can strongly impair myelination via the forced inhibition of multiple targets. [score:5]
Effect of over -expression or inhibition of miR-125a-3p during oligodendroglial differentiation. [score:5]
Almost all mature oligodendrocytes, positive for CC1 express miR-125a-3p, whereas only a subset of NG2 [+] cells express it (Fig. 2d), suggesting a role in the repression of early genes when oligodendrocytes become mature and/or myelinating. [score:5]
Globally, the in vivo and in vitro data suggest multiple developmental roles for miR-125a-3p, that, during embryonic life, is expressed at high levels in neural undifferentiated precursors likely to prevent their untimely commitment, and that, within cells of the oligodendroglial lineage, it could crucially regulate maturation by repressing early transcripts important for the maintenance of OPCs at an undifferentiated state. [score:5]
Over -expression of miR-125a-3p by mimic treatment impairs while its inhibition with an antago-miR stimulates oligodendroglial maturation. [score:5]
All these data support the hypothesis that miR-125a-3p synergistically inhibits different mechanisms that normally promote the expression of myelin genes. [score:5]
When miR-125a-3p was overexpressed by mimic transfection in the presence of T3 (“strong” differentiation protocol), block of terminal maturation was accompanied only by a strong reduction of MAP1B and MBP expression, whereas earlier markers were not affected. [score:5]
How to cite this article: Lecca, D. et al. MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis. [score:5]
Then, we show that, both in rodents and humans, miR-125a-3p is more abundantly expressed in CNS with respect to peripheral tissues, with a higher expression in neurons and oligodendrocytes. [score:5]
When miR-125a-3p overexpression was performed using the “mild” differentiation protocol (i. e., in the absence of T3), OPCs proceeded slower along their lineage and late antigens were not visible, but the number of earlier GPR17 [+] and MAP1B [+] precursors was also diminished, to suggest that, under these conditions, miR-125a-3p can regulate OPC maturation not only downstream but also upstream to GPR17. [score:4]
Our expression studies during brain development showed very high levels of miR-125a-3p at embryonic day E14, mainly in neural precursors. [score:4]
Gene Ontology biological processes (GO BPs) related to oligodendrocyte development are enriched in miR-125a-3p targets. [score:4]
Several other transcripts involved in pathways other than myelination have been so far identified as direct targets of miR-125a-3p. [score:4]
Then, by using STRING, a Gene Ontology (GO) based tool, we found that these targets were significantly clustered in 485 GO biological processes (GO BPs; Supplementary Table S1), suggesting that miR-125a-3p can take part in their regulation. [score:4]
Here we show that miR-125a-3p is up-regulated in the CSF of relapsing MS patients compared to control subjects. [score:3]
Although these findings are obviously not sufficient for proposing miR-125a-3p as a biomarker for MS, our results indeed suggest its potential clinical relevance in this disease. [score:3]
We cannot obviously exclude that the aberrant presence of this miRNA in CSF could also reflect the inflammation state of the CNS during the relapsing-remitting phase of the disease 53, since previous reports have demonstrated the role of miR-125a in immune cells activation 54. [score:3]
These data demonstrate that if differentiation proceeds at a lower speed, miR-125a-3p can also act on early targets, whereas, if differentiation is faster, miRNA can only act on later transcripts that are closer to terminal maturation. [score:3]
As expected, the number of CC1 [+] cells in the adult brain was much higher, but also in this case, virtually all cells expressed miR-125a-3p. [score:3]
Expression of miR-125a-3p in physiological conditions. [score:3]
The fold enrichment in miR-125a-3p was calculated using the following formula as previously described 61: m = genes target in a BP; n = all genes target in the list; M = all genes in a BP; N = all genes in the genome. [score:3]
Expression level of miR-125a-3p was normalized to the U87 snRNA in rat and to the U6 snRNA in human by the ΔCt method. [score:3]
Transfection of primary OPCs with miR-125a-3p mimics and inhibitors. [score:3]
In line with the prediction of our IPA analysis, overexpression of miR-125a-3p resulted in a reduction of Fyn and Nrg1 and Map1b. [score:3]
com/ingenuity), by inserting both miR-125a-3p predicted and validated targets. [score:3]
Since, as mentioned above, Mbp is not a predicted target for miR-125a-3p, we used QIAGEN’s Ingenuity Pathway Analysis tool (IPA [®], QIAGEN Redwood City, www. [score:3]
Specifically, to identify the targets of miR-125a-3p during OPC differentiation in vitro, we took advantage of 4 different markers that identify 4 distinct sequential stages of OPC differentiation, namely: GPR17, O4, MAP1B, and MBP (Fig. 3). [score:3]
Since progressive loss of the ability of OPCs to generate mature oligodendrocytes is a well-known feature of both human MS and other demyelinating diseases 30, we wondered whether miR-125a-3p were also altered in the CSF of MS patients. [score:3]
Coherently, treatment of MS patients with the anti-VLA4 monoclonal antibody (Tysabri) that inhibits inflammatory cell migration to the brain parenchyma and thus favours endothelial integrity, results in decreased blood levels of miR-125a-5p 52. [score:3]
Quantitative real-time PCR analysis revealed a significant upregulation (up to 4 fold) of miR-125a-3p in the active MS group compared to both healthy subjects, AD and inactive MS groups (Fig. 5; p = 0.004 vs. [score:3]
Heterogeneity of OPCs will have to be taken in account also when transposing our in vitro results to human MS subjects showing increased levels of miR-125a-3p in CSF; however, this does not invalidate the biological importance of our findings in MS patients, since a biomarker is defined as a proxy that allows remote and early detection of a biological process (i. e., disease) regardless of its mechanistic role in the condition being diagnosed 57. [score:3]
MiR-125a-3p is up-regulated in cerebrospinal fluid of MS patients. [score:3]
Cells were stained for the selected markers 48 h after transfection of miR-125a-3p mimic or inhibitor, in the presence or in the absence of the T3 hormone. [score:3]
The fold enrichment in miR-125a-3p was calculated using the following formula as previously described 61:m = genes target in a BP; n = all genes target in the list; M = all genes in a BP; N = all genes in the genome. [score:3]
Then, to assess if the expression timing of miR-125a-3p indeed changes during oligodendrocyte maturation, we used cultured OPCs to measure its expression during their in vitro differentiation. [score:3]
Time-regulated expression of MiR-125a-3p in cultured OPCs. [score:3]
To confirm the importance of miR-125a-3p in OPC maturation, in a parallel experiment, OPCs maintained under the same culture conditions were transfected with a hairpin inhibitor RNA that specifically inactivates miR-125a-3p. [score:3]
Then, we focused on oligodendrocytes, and evaluated whether miR-125a-3p is preferentially expressed in early OPCs expressing the proteoglycan NG2, or in more mature CC1 [+] oligodendrocytes. [score:3]
In postnatal brain, some cells already expressed CC1 and virtually all of them were also decorated with the probe for miR-125a-3p (Fig. 2d). [score:3]
Expression of miR-125a-3p in the cerebrospinal fluid of MS patients. [score:3]
STRING database 59 was used to obtain a list of the Gene Ontology 60 biological processes (GO BPs) significantly enriched (p value < 0.05) for miR-125a-3p targets. [score:3]
In this respect, our data on the role of miR-125a-3p on OPCs maturation under “strong” or “mild” differentiation paradigms unveil that myelination may be regulated in different ways even by the same miRNA depending upon distinct pathophysiological conditions. [score:2]
MiR-125a-3p potentially targets players involved in oligodendrocyte differentiation. [score:2]
Then, we asked whether miR-125a-3p is regulated in rat developing brain. [score:2]
The identification of miR-125a-3p as a modulator of oligodendrocyte differentiation provide new findings about the complex regulation of myelination processes and it is conceivable that an antago-miRNA specific for this miRNA may help in promoting oligodendrocyte maturation in diseases characterized by impaired myelin repair. [score:2]
MiR-125a-3p acts on multiple target transcripts involved in oligodendrocytes maturation. [score:2]
We performed the same analysis on human samples, and, among the analysed tissues, miR-125a-3p was found mainly expressed in brain tissues, with a significant enrichment in frontal cortex compared to whole brain and also in brain stem and corpus striatum (Supplementary Fig. S1). [score:2]
A significant increase in the relative expression of miR-125a-3p was found by RT-PCR in the cerebrospinal fluid of active MS patients (n = 11) compared to control (C; n = 13; p value = 0.004), Alzheimer (AD; n = 17; p value = 0.004) and inactive MS (n = 19; [§]p = 0.0545) groups. [score:2]
Histograms in blue show the significant GO BPs enriched in miR-125a-3p target transcripts (fold enrichment compared to expected value = 1; see left axis). [score:2]
MiR-125a-3p mimics or hairpin inhibitors (Dharmacon) were transfected at the final concentration of 50 nM. [score:2]
In agreement with previous findings that miR-125a-3p is a brain-enriched miRNA, we highlighted that many GO BPs include nervous system development, neurogenesis, glial cell differentiation, myelination, and oligodendrocyte differentiation (Fig. 1). [score:2]
Expression level of miR-125a-3p was analyzed with TaqMan [®] MicroRNA Assays and normalized to spiked-in cel-miR-39 by the ΔCt method. [score:2]
Here, we describe miR-125a-3p as a new regulator of oligodendroglial differentiation with potential roles in myelination and in defective remyelination. [score:2]
Demographic data and miR-125a-3p log2 fold increase by diagnostic group. [score:1]
For all of them, we calculated and reported the fold enrichment in miR-125a-3p targets (see equation (1) in) and we found that the BPs related to oligodendrocyte differentiation have a higher enrichment among all the CNS-related BPs, strongly supporting our hypothesis. [score:1]
day 0. To evaluate the time -dependent effects of either the overexpression or the silencing of miR-125a-3p on OPC maturation 4 different markers of progressive differentiation stages were analysed by immunocytochemistry, GPR17 and O4 (which label pre-oligodendrocytes), MAP1B (which labels a slight more advanced stage) and MBP (which labels terminally differentiated cells). [score:1]
To evaluate the possible role of miR-125a-3p in OPC differentiation, we overexpressed it by transfecting cells with a specific miR-125a-3p mimic the same day of growth factors withdrawal (corresponding to day 0 in Fig. 2e) when the endogenous levels of miR-125a-3p were low. [score:1]
In this perspective, our data could serve as a basis for further studies on larger cohort of patients to validate miR-125a-3p as a biomarker for different stages of MS, providing a previously unrecognized venue for medical interventions. [score:1]
This increase could be explained by passive release of miR-125a-3p from neural cells such as neurons or oligodendrocytes undergoing destruction in active MS patients. [score:1]
Mo del representing the connections between miR-125a-3p and MBP. [score:1]
In this respect, our results suggest that also miR-125a-3p could have a Janus-like role in OPC maturation, acting as a repressor in the early phases of the maturation and likely as a positive factor in later phases, repressing genes that could impair terminal maturation. [score:1]
However, studies in the literature did not analyze separately the specific role of either the −5p and the −3p strand, since they often refer to miR-125a as the double-stranded precursor miRNA 9 10, and this may be misleading. [score:1]
While the number of cells positive for GPR17 and O4 were unaltered (Fig. 3d,e), the number of MAP1B [+] cells was reduced by approximately the 50% after mimic miR-125a-3p treatment (Fig. 3f), suggesting inactivation of transcripts specifically involved in the progression between the O4 and the MAP1B stage. [score:1]
In embryonic brain, miR-125a-3p was found widespread in the whole parenchyma with a higher signal in the ventricular zone (Fig. 2c), where it mostly co-localized with Olig2, which, at this stage, labels a pool of precursor cells that will give rise to both OPCs and neurons 21, and to a lower extent with Nestin. [score:1]
Pre-hybridization was carried out for 2 hours at room temperature, followed by hybridization with scramble/miR-125a-3p DIG-LNA probes (20 nM; Exiqon) overnight at 55 °C. [score:1]
Here we propose a mechanistic role for miR-125a-3p based on data obtained on cultured rodent OPCs. [score:1]
To assess the expression of miR-125a-3p in the CNS, by means of real-time PCR we measured its levels in several rodent and human tissues and cells. [score:1]
Globally, these data suggest that miR-125a-3p exerts a silencing effect on transcripts typical of OPC differentiation stages that are upstream to MAP1B but downstream to GPR17 and O4. [score:1]
Our analysis showed that indeed, miR-125a-3p it is more abundantly present in the CNS of both rat and human. [score:1]
To this aim, we performed a triple immunofluorescence staining using the same ISH technique described above for miR-125a-3p in parallel with anti-NG2 and anti-CC1 antibodies in both postnatal (P7) and adult brains, in particular, corpus callosum, where a large number of oligodendrocytes could be analysed. [score:1]
In a previous study, the-5p arm of miR-125a was found to act as a key regulator of brain endothelial integrity and its levels to be increased in MS brain lesions as compared to surrounding normal appearing white matter 51. [score:1]
We thus measured miR-125a-3p levels in CSF samples from 30 MS patients (28 patients with the relapsing-remitting and 2 with the secondary-progressive form), 11 of which had clinically or neuroradiologically active disease (active lesions) at the time of CSF withdrawal. [score:1]
Both in P7 and adult brains, co-localization between miR-125a-3p and NG2 was also found, but only in a subpopulation of cells, with a further trend toward a decrease in the adult, suggesting that miR-125a-3p serves a more critical function in mature oligodendrocytes. [score:1]
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In hepatocellular carcinoma cells, ectopic expression of miR-125a resulted in inhibition of proliferation and metastases, caused by miR-125a's ability to target matrix metalloproteinase 11 (MMP11) and vascular endothelial growth factor A [19]. [score:7]
When comparing miR-125a-3p -overexpressing cells to controls, we were able to show a significant reduction in known migration parameters as track displacement and mean track speed, suggesting that overexpression of miR-125a-3p inhibited the cells' motility. [score:7]
We show that over expression of miR-125a-3p led to an increase in E-cadherin expression, as well as a decrease in the expression of MT1-MMP, a matrix metalloproteinase known to induce EMT in prostate cancer cells [29]. [score:7]
The interaction between Fyn and Akt was shown to be reciprocal; Fyn induced Akt activation in an indirect manner [37] and hampered the activation of Akt when it was down-regulated in HEK 293T cells [22] We demonstrate that overexpression of miR-125a-3p led to a reduction in the activity of Akt, which may have an impact on both proliferation and migration via signaling pathways that involve Fyn. [score:7]
Following our analysis of non-cancerous HEK 293T cells at which the regulation of Fyn expression by miR-125a-3p has been established [22], we confirmed that this regulation applies also in prostate cancer cell. [score:5]
We demonstrated that over -expression of miR-125a-3p inhibited the migratory capability of PC3 cells. [score:5]
Furthermore, we also noticed that the morphology of miR-125a-3p -overexpressing cells differed from that of control cells; the miR-125a-3p -overexpressing cells acquired a round shape that resembled epithelial cells rather than mesenchymal cells. [score:5]
Ectopic expression of miR-125a resulted in overexpression of miR-125a-3p. [score:5]
Comparing the cancerous tissue with adjacent non-cancerous tissue revealed an inverse correlation between miR-125a-3p expression and Gleason score of the tissue; we dichotomously defined the samples according to the pathological known score of “risk of recurrence” and could delineate an inverse correlation between tumor differentiation and miR-125a expression (Figure 6A; p<0.05 Wilcoxon test). [score:5]
In light of the above, along with studies that established the involvement of Fyn in processes of cellular motility in prostate cancer [10, 11], we demonstrate in the current study that miR-125a-3p down-regulates cellular pathways that account for proliferation and migration of prostate cancer cells, and portray its regulation of key proteins involved in these pathways. [score:5]
miR-125a-3p suppresses the level of expression of Fyn mRNA and protein, as well as of its downstream effectors. [score:5]
This assumption is based also on our results indicating that miR-125a-3p -overexpressing viable cells present reduced migration in transwell assay as well as down-regulation of migration-correlated migratory proteins. [score:5]
In a former study performed on human embryonic kidney (HEK 293T) cell-line, we have established the role of miR-125a-3p, an isoform derived from the 3′ arm of pre-miR-125a, in regulating cell migration and proliferation accomplished by targeting Fyn [22]. [score:4]
However, it was suggested that this effect of miR-125a-3p is mediated by miR-125a-3p -induced decrease in the expression of RhoA, a well-known regulator of actin cytoskeletal and adhesion dynamics [31]. [score:4]
Our results are compatible with former studies that indicated down-regulation of miR-125a-3p in human gastric and lung cancer [41, 42]. [score:4]
Figure 1 (A) Endogenous and manipulated expression of miR-125a-3p. [score:3]
To further analyze the morpho-kinetic parameters of migration in miR-125a-3p overexpressing cells, we employed confocal live imaging. [score:3]
Remarkably, cells overexpressing miR-125a-3p presented a 28% decrease in their mean track speed (Figure 3B) and their track displacement was ~30% shorter than that of control cells (Figure 3C). [score:3]
Initially we demonstrated that miR-125a-3p is endogenously expressed in PC3 cells. [score:3]
With the aid of a confocal microscope we observed an impairment of the actin rearrangement in cells overexpressing miR-125a-3p, along with a decrease in their membrane protrusions which are necessary for cell migration (Figure 5A). [score:3]
Thus, miR-125a-3p may represent a new plausible therapeutic target to reduce metastatic potential of prostate cancer and to define high risk patients for preventive therapy. [score:3]
To further understand the molecular mechanism by which miR-125a-3p inhibits migration, we examined its effect on several key proteins. [score:3]
We further showed that overexpression of miR-125a-3p hampers the focal adhesion sites. [score:3]
We also show an inverse correlation between the expression of miR-125a-3p and the Gleason score in tissue samples obtained from patients diagnosed with prostate cancer. [score:3]
The expression of miR-125a-3p was studied in Formalin-Fixed, Paraffin-Embedded (FFPE) human prostate cancer samples. [score:3]
Other targets of miR-125a-3p as chemokine (C-C motif) ligand 4 and IGF-2, may also be involved in this process, as has already been suggested [41]. [score:3]
The fact that miR-125a-3p reduced the cells' migratory capability and the activity of FAK and paxillin, two proteins that serve as anchors for actin filaments [23], prompted us to examine whether the inhibition of cell migration by miR-125a-3p was mediated by alterations in actin cytoskeleton. [score:3]
Since high Gleason score correlates with higher risk for disease recurrence and metastatic potential caused by primary tumor cells spread, miR-125a-3p that plays a key role in modulating migration pathways accounting for the high metastatic potential, may be of high clinical relevance. [score:3]
The ability of miR-125a-3p to hamper the actin cytoskeleton and thereby to inhibit cells migration has also been shown in lung cancer cells [21]. [score:3]
Moreover, we also observed a phenotypic change in the shape of the cells: control cells presented a more elongated shape, resembling epithelial to mesenchymal transition (EMT) phenotype, whereas cells overexpressing miR-125a-3p acquired a round shape, resembling epithelial phenotype (Figure 3D). [score:3]
A significant decrease in the migratory capacity of the cells was observed 24 hours after performing the scratch; miR-125a-3p overexpressing cells covered only 48% of the scratch area whereas control cells migrated and covered the entire scratch area (Figure 2A). [score:3]
Over -expression of miR-125a impaired migration and invasion of breast cancer cells [18]. [score:3]
Graphs summarize (B) Track lengh, (C) Track speed and (D) Elipticity of 111 control cells and 86 miR-125a-3p -overexpressing cells. [score:3]
We showed that miR-125a-3p reduced the expression level of Fyn mRNA and protein (Figure 4A and B), respectively. [score:3]
The expression pattern of miR-125a-3p was analyzed in biopsies of prostate tissue samples from 20 patients diagnosed with prostate cancer. [score:3]
miRNAs were extracted from the cancerous prostate tissue and from adjacent non-cancerous tissue using miRNeasy FFPE kit (Qiagene, GmbH, Hilden, Germany) according to the manufacturer's instructions and the expression of miR-125a-3p was determined by qPCR as described earlier. [score:3]
A' and B'- lower magnification photos of control and miR-125a-3p overexpressing cells; A'' and B''- higher magnification photos, respectively. [score:3]
WB analysis indicated a 26% and 32% decrease in the phosphorylation state of FAK and paxillin in miR-125a-3p -overexpressing cells (Figure 4C and D), respectively. [score:3]
Herein we confirm an impairment of F-actin organization resulting in disarrangement of actin-derived protrusions in cells overexpressing miR-125a-3p; a phenomenon that may underlie the impairment of the migratory capability as observed in our study. [score:3]
Reinforced by western blot (WB) analysis that showed reduced activity of Akt-1 protein, an anti-apoptotic factor, in cells overexpressing miR-125a-3p (Figure 1D), our results imply that miR-125a-3p induces apoptosis. [score:3]
This result corresponds highly with the inverse correlation of miR-125a-3p expression and Gleason score in human prostate cancer tissues. [score:3]
Figure 6 The expression of miR-125a-3p was studied in Formalin-Fixed, Paraffin-Embedded (FFPE) human prostate cancer samples. [score:3]
Since bioinformatics does not predict FAK, paxillin or Akt as miR-125a-3p targets, we can conclude that miR-125a-3p may exert its effect on these proteins via Fyn. [score:3]
miR-125a-3p expression is reduced in human prostate cancer. [score:3]
miR-125a-3p may also regulate cell migration by an ancillary pathway - the PI3K/Akt signaling pathway. [score:2]
These results suggest that miR-125a-3p plays a key role in modulating cells migration by a mechanism that involves regulation of EMT. [score:2]
The results, of 17 patients, are presented as the fold change of the expression of miR-125a-3p in tumor sample compared to its normal control (non pathologic sample). [score:2]
Finally, we sought for clinical implication for our findings, and therefore analyzed the expression pattern of miR-125a-3p in prostate tissue samples retrieved from patients diagnosed with prostate cancer and compared them with the adjacent non-cancerous tissue. [score:2]
We found a 34% decrease in the number of miR-125a-3p -overexpressing cells that migrated for 6-8 hours through the pores towards the serum underneath the plate, compared to control cells (Figure 2B). [score:2]
We find the interpretation that miR-125a-3p hampers cells migratory capability by inducing apoptosis, as a plausible one, though we assume that this effect is not a direct result of apoptosis because the effect of miR-125a-3p on cells migration was greater than its effect on apoptosis. [score:2]
miRNA-125a (miR-125a) was demonstrated to regulate major cellular processes in several types of cancer cells. [score:2]
Our results imply a role for miR-125a-3p in regulating cell migration, possibly, in part, via a Fyn dependent manner. [score:2]
Moreover, we reported that miR-125a-3p reduced the activity of Fyn-downstream proteins as FAK, paxillin and Akt. [score:1]
PC3 cells were co -transfected with either: miR-125a-3p and GFP plasmid or an empty miR-Vec and RFP plasmid (control). [score:1]
Figure 3 PC3 cells were co -transfected with either: miR-125a-3p and GFP plasmid or an empty miR-Vec and RFP plasmid (control). [score:1]
In view of former evidence of miRNA's critical role in tumor invasion and metastasis [24] we focused on studying the potential involvement of miR-125a-3p in cellular pathways leading to motility and migration of cancer cells. [score:1]
We observed an inverse correlation between miR-125a-3p and Gleason score. [score:1]
PC3 cells were seeded onto coverslips and (A) co -transfected with miR-125a-3p and GFP (bottom panel; green) or with empty miR-Vec and GFP (control; top panel; green). [score:1]
Future studies should address the cellular mechanism underlying miR-125a-3p involvement in modulating migratory capacity of prostate cancer cells and its potential role in an in vivo mo del. [score:1]
A role of miR-125a in the process of invasion and migration has also been implied in gastric and lung cancer cells [20, 21]. [score:1]
This implies that miR-125a-3p reduces the cell membrane protrusions probably by impairing the dynamic interplay between the actin cytoskeleton and cell adhesion sites, thus leading to reduced cell motility. [score:1]
miR-125a-3p impairs the actin cytoskeleton. [score:1]
Figure 4 PC3 cells, transfected with miR-125a-3p or with empty vector (control), were cultured for 48 hours. [score:1]
In this study we elucidate the role of miR-125a-3p in cellular pathways accounted for motility and migration of prostate cancer cells. [score:1]
However, since a scratch assay does not take into account the apoptotic cells, we performed a transwell assay in which it is possible to exclude the apoptotic cells by seeding a similar number of viable control or miR-125a-3p -overexpressing cells. [score:1]
miR-125a-3p impairs the morpho-kinetic coordinated collective migration. [score:1]
miR-125a-3p is reduced in prostate cancer samples. [score:1]
Taken together, our results suggest that miR-125a-3p reduces cell membrane protrusions probably by impairing the dynamic interplay between the actin cytoskeleton and cell adhesion sites, leading to reduction in cell motility. [score:1]
PC3 cells were seeded in 6-well plate and then co -transfected with miR-125a-3p together with a GFP plasmid or with an empty miR-Vec together with an RFP plasmid (control cells). [score:1]
PC3 cells, transfected with miR-125a-3p or with empty vector (control), were cultured for 48 hours. [score:1]
miR-125a-3p impairs cell cycle, viability and induces apoptosis. [score:1]
We, therefore suggest that miR-125a-3p affects both proliferation and migration via partially-linked pathways. [score:1]
To this end, cells were co -transfected with control vector and an RFP plasmid (Figure 3A, left), or with miR-125a-3p and a GFP plasmid (Figure 3A, right; supplementary I). [score:1]
We therefore transfected PC3 cells with either miR-125a-3p and GFP or with control vector and GFP (as a control), and then stained for actin filaments (F-actin) using FITC-conjugated phalloidin. [score:1]
Transfection with a control plasmid (an empty miR-Vec that contained no miRNA; see Methods) had no effect on the level of miR-125a-3p and was therefore used as a transfection control in the following experiments (Figure 1A). [score:1]
Taken together, our results show that miR-125a-3p impairs the rearrangement of the actin filaments, the activity of FAK and paxillin [23, 34], and the localization of paxillin to the focal adhesions sites at the tips of the actin filaments. [score:1]
We demonstrate herein that miR-125a-3p remarkably impaired the migratory capability of PC3 cells, as seen by dynamic confocal imaging of miR-125a-3p transfected PC3 cells. [score:1]
Figure 5 PC3 cells were seeded onto coverslips and (A) co -transfected with miR-125a-3p and GFP (bottom panel; green) or with empty miR-Vec and GFP (control; top panel; green). [score:1]
miR-125a-3p alters migration and morphology of PC3 cells. [score:1]
In order to evaluate the effect of miR-125a-3p on cells' viability, we preformed FACS analysis, which indicated that overexpression of miR-125a-3p led to a 10 fold increase in the percentage of cells at the sub G1 stage whereas other stages of the cell cycle were not affected (Figure 1B). [score:1]
The effect of miR-125a-3p on hallmark genes in prostate cancer. [score:1]
Our results imply that high levels of miR-125a-3p might interfere with EMT in prostate cancer cells. [score:1]
Migration assays -Transwell assay - PC3 cells (overexpressing miR-125a-3p or empty miR-Vec) were stained with trypan blue and counted in a Countess automated cell counter machine (Invitrogen). [score:1]
Our results imply that miR-125a-3p modulates molecular pathways of motility and migration in prostate cancer cells. [score:1]
All parameters collected along the experiments were analyzed for each cell and only then, group analysis (control or miR-125a-3p) was performed. [score:1]
miR-125a-3p impairs cells motility. [score:1]
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5
[+] score: 210
We showed that (1) both FUT5 and FUT6 were highly expressed in CRC tissues and cell lines, which enhanced the proliferation, migration, invasion and angiogenesis capacity of CRC cells and tumour growth in vivo, and (2) miR-125a-3p was significantly downregulated in CRC tissues and cell lines, as miR-125a-3p expression could greatly inhibit migration, invasion and angiogenesis of CRC cells and tumour growth in vivo, further improving survival. [score:10]
In the CCK8 cell proliferation assay, we found that cell proliferation was promoted after miR-125a-3p knockdown or overexpression of FUT5 and FUT6 in SW480 cells (Figures 3a and b), whereas inhibition of FUT5 and FUT6 or overexpression of miR-125a-3p could suppress the proliferation of SW620 cells (Figures 3c and d). [score:9]
In conclusion, our study demonstrated that overexpression of miR-125a-3p attenuated the migration, invasion and angiogenesis of CRC cell lines and inhibited tumour growth in vivo by affecting FUT5 or FUT6 regulated expression through the PI3K/Akt signalling pathway. [score:8]
The expression of miR-125a-3p was significantly decreased in CRC tissues compared with normal tissue (Figure 1a), whereas the expression levels of FUT5 and FUT6 were significantly upregulated in cancer tissue (Figures 1b and c). [score:7]
In vitro, using functional analyses, we found that overexpression of miR-125a-3p inhibited cell proliferation migration, invasion and development of CRC cells. [score:6]
These results imply that low expression of miR-125a-3p and its associated expression of FUT5 and FUT6 may be related to CRC development. [score:6]
On the basis of inverse relationship between FUT5 or FUT6 expression and miR-125a-3p in CRC tissues, we hypothesised that FUT5 and FUT6 may be direct targets of miR-125a-3p. [score:6]
In vivo, overexpression of miR-125a-3p inhibited tumour growth. [score:5]
On the other hand, expression of FUT5 or FUT6 was blocked by overexpression of miR-125a-3p, which similar to effect of FUT5 shRNA or FUT6 shRNA in SW620 (Figures 2h and j). [score:5]
These results indicate that inhibition of miR-125a-3p or overexpression of FUT5 and FUT6 can promote proliferation and migration in CRC cells. [score:5]
To gain mechanistic insight into how FUT5 and FUT6 regulated by miR-125a-3p, we used public prediction algorithms, Targetscan and microRNA. [score:4]
Taken together, we conclude that both FUT5 and FUT6 are direct targets of miR-125a-3p. [score:4]
FUT5 and FUT6 are direct targets of miR-125a-3p in CRC cells. [score:4]
In summary, FUT5 and FU6 were found to be novel direct targets of miR-125a-3p. [score:4]
We found that anti-miR-125a-3p transfection led to a significant increase in FUT5 or FUT6 expression, which similarly to affected FUT5 or FUT6 regulation (Figures 2d and f). [score:4]
These data suggest that overexpression of FUT5 or FUT6 induced by miR-125a-3p promoted the invasion ability of CRC cells and development of tumours. [score:4]
Furthermore, the effect of miR-125a-3p inhibitors can be reversed by transfection with FUT5 shRNA or FUT6 shRNA in SW480 cells. [score:3]
To provide evidence for this prediction, qPCR was used to analyse FUT5 and FUT6 expression in SW480 cells transfected with anti-miR-125a-3p, FUT5 or FUT6. [score:3]
Consistently, miR-125a-3p and miR-125a-5p inhibit the invasion and migration of lung cancer cells. [score:3]
[35] miRNA-125a-3p reduces cell proliferation and migration by targeting Fyn associated with several types of cancer. [score:3]
In SW620 xenograft tumours, miR-125a-3p overexpressing tumours showed low FUT5 and FUT6 protein levels, and FUT5 or FUT6 protein reduced in the SW620/FUT5 shRNA or SW620/FUT6 shRNA group (Supplementary Figure 1; Figures 5i and j). [score:3]
Furthermore, FUT5 and FUT6 overexpression dramatically attenuated the effect of miR-125a-3p, whereas this effect of FUT5 or FUT6 can be reversed by transfection with miR-125a-3p -mimics. [score:3]
In this study, we found that miR-125a-3p expression was significantly decreased in CRC tissues by qPCR analysis. [score:3]
Furthermore, miR-125a-3p was inversely correlated with FUT5 and FUT6 expression, which dramatically attenuated effect of FUT5 and FUT6. [score:3]
miR-125a-3p -mimics and WT or mutant target sequence were co -transfected into HEK293T cells via Lipofectamine 2000. [score:3]
First, we analysed the expression of miR-125a-3p via a miRNA microarray (data not shown) in SW480 (poorly invasive) and SW620 (highly invasive) cells. [score:3]
Through data analysis, we found an inverse relationship between FUT5 or FUT6 expression and miR-125a-3p in CRC tissues (Figures 1d and e). [score:3]
Next, we a used dual-luciferase reporter assay to test whether FUT5 and FUT6 are direct targets of miR-125a-3p. [score:3]
In the tissues with low of miR-125a-3p, FUT5 and FUT6 expression was high (Figure 1f). [score:3]
The expression of mature miR-125a-3p was determined by qPCR with the mirVanaTM qPCR microRNA Detection Kit (Ambion, Austin, TX, USA) according to manufacturer’s protocol and relative to U6-small nuclear RNA. [score:3]
The results showed that co-transfection of HEK293T cells with miR-125a-3p -mimics inhibits WT FUT5 3′-UTR regulated luciferase activity compared with the control but did not affect the luciferase activity of the MT FUT5 3′-UTR reporter (Figure 2l). [score:3]
For example, BCL2, BCL2L12 and MCL1 are target genes of miR-125a-5p in CRC. [score:3]
miR-125a-3p -mimics, negative control oligonucleotides (miR-NC) and miR-125a-3p inhibitors (anti-miR-125a-3p) were purchased from RiboBio (Guangzhou, China). [score:3]
Similar to the effects of SW620 cells transfected with miR-125a-3p -mimics, FUT5 shRNA or FUT6 shRNA impaired colony formation, and miR-125a-3p -dependent inhibition of FUT5 and FUT6 was rescued by reintroduction of FUT5 or FUT6 in SW620 cells (Figures 3g and h). [score:3]
We hypothesised that FUT5 and FUT6 may be target genes of miRNA-125a-3p. [score:3]
[34] Moreover, miR-125a-5p inhibits cell proliferation in CRC. [score:3]
[31] The miR-125a family suppresses tumour growth in renal cell carcinoma [32] and breast tumourigenesis, [33] and is increasingly recognised as an important anti-oncogene. [score:3]
To investigate the correlation of FUT5 and FUT6 expression with miR-125a-3p in CRC tissues, we examined miR-125a-3p, FUT5 and FUT6 expression from 35 pairs of CRC patients by qPCR (Supplementary Table 1). [score:3]
In this study, we investigated whether miR-125a-3p has an inhibitory effect on CRC via targeting both FUT5 and FUT6. [score:3]
With regard to overall survival, patients with low miR-125a-3p expression had a significantly poorer prognosis (Figure 1g). [score:3]
org and initially identified FUT5 and FUT6 as potential miR-125a-3p targeted genes. [score:3]
The miR-125a-3p/FUT5-FUT6 axis regulates the invasion and angiogenesis of CRC cells. [score:2]
Hence, our findings revealed that the miR-125a-3p/FUT5-FUT6 axis was involved in PI3K/Akt pathway activation, which regulates the proliferation, invasion and angiogenesis ability of CRC cells. [score:2]
Similarly, the luciferase activity assay showed that overexpression of miR-125a-3p significantly reduced the luciferase activity of WT FUT6 3′-UTR reporter plasmids, but had no effect on MT FUT6 3′-UTR reporters (Figure 2m). [score:2]
The expression of miR-125a-3p was low in SW620 cells compared with SW480 cells. [score:2]
We found that the miR-125a-3p/FUT5-FUT6 axis mediated the PI3K/Akt signalling pathway, which regulated the proliferation, invasion and angiogenesis ability of CRC cells. [score:2]
The miR-125a-3p/FUT5-FUT6 axis regulates CRC cell growth in vivo. [score:2]
Combined with results of the bioinformatics analysis and luciferase activity assays, both FUT5 and FUT6 were identified as target genes of miR-125a-3p. [score:2]
Altogether, these findings confirmed that FUT5 and FUT6 possess tumour stimulating activities in CRC tumours, which was regulated by miR-125a-3p. [score:2]
The sequences of miR-125a-3p inhibitor primers were as follows: 5′-GGCUCCCAAGAACCUCACCUGU-3′. [score:2]
The results showed that SW480 cells transfected with anti-miR-125a-3p or the FUT5 or FUT6 group had increased invasion compared with the control (Figures 4a and b), whereas the expression of miR-125a-3p -mimics, FUT5 shRNA or FUT6 shRNA reduced the invasion ability of SW620 cells (Figures 4c and d). [score:2]
The miR-125a-3p/FUT5-FUT6 axis regulates cell proliferation and migration in CRC. [score:2]
Similar results were obtained by qPCR analysis, which showed that miR-125a-3p expression was markedly reduced in SW620 cells compared with SW480 and FHC (Figure 2a). [score:2]
Mimics and control oligonucleotides for miR-125a-3p were obtained from RiboBio (GenePharma, Shanghai, China). [score:1]
To test the effects of the miR-125a-3p/FUT5-FUT6 axis on PI3K/Akt pathway, we used western blot analysis. [score:1]
miR-125a-3p -mimics were transfected into SW620 cells, and anti-miR-125a-3p was transfected into SW480 cells. [score:1]
In SW480 xenograft tumours, FUT5 or FUT6 protein increased in the SW480/FUT5 or SW480/FUT6 group and anti-miR-125a-3p group (Figures 5d and e). [score:1]
The length of tubes was significantly increased by proangiogenic stimuli from the supernatant of the anti-miR-125a-3p, FUT5 or FUT6 group (Figures 4e and f), and opposing results were found in the miR-125a-3p -mimics, FUT5 shRNA or FUT6 shRNA group (Figures 4g and h). [score:1]
Therefore, we tested the influence of the miR-125a-3p/FUT5-FUT6 axis on activation of the PI3K/Akt signalling pathway by the western blot. [score:1]
[35] We hypothesised that miR-125a-3p may also have similar effects in CRC. [score:1]
Our data suggest that miR-125a-3p may be an important anti-oncogene in CRC. [score:1]
Collectively, these results suggest that the miR-125a-3p/FUT5-FUT6 axis affected the PI3K/Akt pathway. [score:1]
The effect of anti-miR-125a-3p or miR-125a-3p -mimics was rescued by FUT5 and FUT6 or FUT5 shRNA and FUT6 shRNA, respectively. [score:1]
The results demonstrated that the miR-125a-3p/FUT5-FUT6 axis markedly effects Akt phosphorylation. [score:1]
We simultaneously, we used a miRNA delivery method to increase or reduce miR-125a-3p in tumour cells of mouse xenografts. [score:1]
In addition, PI3K110a, Akt Thr308, Akt Ser473 and NF-kB in SW620 cells transfected with miR-125a-3p -mimics, FUT5 shRNA or FUT6 shRNA were significantly reduced (Figure 6b). [score:1]
miR-125a-3p is inversely associated with FUT5 and FUT6 in CRC tissues. [score:1]
miR-125a-3p may represent a novel strategy with biological significance and diagnostic and prognostic value. [score:1]
The data indicated that wound closure in the anti-miR-125a-3p, FUT5 or FUT6 group was significantly increased in SW480 cells (Figures 3i and j). [score:1]
In summary, our work suggests that miR-125a-3p is a potent anti-oncogene of CRC. [score:1]
The miR-125a-3p/FUT5-FUT6 axis mediates activity of the PI3K/Akt signalling pathway in CRC cells. [score:1]
To assess the influence of the miR-125a-3p/FUT5-FUT6 axis in tumour development, we utilised an endothelial tube formation assay. [score:1]
Western blot showed that PI3K p110a or phosphorylation of Akt at Thr308 and Ser473 and NF-kB were greatly enhanced in SW480 treated with FUT5, FUT6 or anti-miR-125a-3p. [score:1]
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6
[+] score: 207
miR-125a-3p and miR-483-5p are upregulated during the differentiation of hADSCs, and target proteins are downregulated in MSL. [score:9]
The results showed that the miR-125a-3p mimic significantly downregulated RhoA and its downstream factor ROCK1 and ROCK2; conversely, the miR-125a-3p inhibitor significantly upregulated RhoA, ROCK1 and ROCK2 (Fig. 3C). [score:9]
In hADSCs, miR-125a-3p inhibits RhoA, resulting in decreased ROCK1 expression, which inhibits n-T-ERK1/2 and n-p-ERK1/2 in the nucleus. [score:7]
To determine whether miR-483-5p regulates the RhoA/ROCK1/ERK1 pathway, we compared the expression levels of these proteins in hADSCs transfected with the miR-125a-3p inhibitor, miR-483-5p mimic, or cotransfection of the miR-125a-3p inhibitor and miR-483-5p mimic, and found that cotransfection did not change the T-ERK1/2 or T-p-ERK1/2 levels but apparently changed the n-T-ERK1/2 and n-p-ERK1/2 levels. [score:7]
Similar to the in vitro experiments, miR-125a did not affect T-ERK1/2 or T-p-ERK1/2 expression but decreased RhoA and ROCK1 expression, accompanied with decreased n-T-ERK1/2 and n-p-ERK1/2 expression. [score:7]
Moreover, n-T-ERK1/2 and n-p-ERK1/2 were downregulated in the cotransfected group compared to that of the miR-125a-3p inhibitor group while upregulated compared to that of the miR-483-5p mimic group (Fig. 5D). [score:7]
Next, after each group was induced to mature adipocytes for 12 days, C/EBPα, PPARγ, and FABP4 were upregulated by the agomir of miR-125a-3p or miR-483-5p; while they were downregulated by the antagomir of miR-125a-3p or miR-483-5p (Fig. 2D,E). [score:7]
In comparison to the control and miR-125a-3p inhibitor, cotransfection with the miR-125a-3p inhibitor and miR-483-5p mimic resulted in decreased expression of T-ERK1/2 and T-p-ERK1/2 to the levels of the miR-483-5p mimic group (Fig. 5C). [score:7]
Consistent with the previous observation in mouse and human MSCs 16, we found that miR-125a-3p expression was gradually upregulated in adipogenesis. [score:6]
To determine whether miR-125a-3p and miR-483-5p jointly regulate the activity of the RhoA/ROCK1/ERK1/2 pathway, we first detected the expression of T-ERK1/2, T-p-ERK1/2, n-T-ERK1/2, and n-p-ERK1/2 following transfection of hADSCs with the mimic or inhibitor of miR-125a-3p. [score:6]
n-T-ERK1/2 and n-p-ERK1/2 were downregulated in the LV-miR-125a and LV-miR-483 groups, and even greater downregulation was observed in the cotransfection group compared to the LV-miR-125a and LV-miR-483 groups (Fig. 6G). [score:6]
To generate hsa-miR-125a and hsa-miR-483 lentiviral expression plasmids, 268-bp and 273-bp sequences containing pre-hsa-miR-125a or pre-hsa-miR-483 were synthesized and cloned into lentiviral expression vector pGC-FU (GeneChem, Shanghai, China), respectively. [score:5]
In the de novo adipose tissues of LV-miR-125a or LV-miR-483 group, we found that miR-125a-3p and miR-483-5p expression was significantly higher than miR-125a-5p and miR-483-3p expression (Fig. 6C). [score:5]
Next, we cotransfected the miR-125a-3p inhibitor and miR-483-5p mimic to test ERK1/2 expression in hADSCs. [score:5]
Transfection with either the mimic or inhibitor of miR-125a-3p did not alter the T-ERK1/2 or T-p-ERK1/2 expression levels (Fig. 5A). [score:5]
In this study, we discovered that 18 miRs were upregulated in the SAT of MSL patients and that miR-125a-3p or miR-483-5p significantly promoted adipogenesis via the RhoA/ROCK1/ERK1/2 pathway (Fig. 7). [score:4]
These results clearly demonstrated that RhoA and ERK1 are the direct target genes of miR-125a-3p and miR-483-5p, respectively. [score:4]
miR-125a-5p, another mature sequence of miR-125a, has been found to be downregulated in the epididymal fat pads of leptin -deficient ob/ob mice. [score:4]
The miR-125a-3p and miR-483-5p expression levels were detected by quantitative real-time PCR at days 0, 6, and 12. [score:3]
RhoA and ERK1 are the respective target genes of miR-125a-3p and miR-483-5p. [score:3]
To investigate the expression tendency of miR-125a-3p and miR-483-5p during hADSC differentiation, we used real-time PCR to detect the miR-125a-3p and miR-483-5p expression at days 0, 6, and 12 during the induction to mature adipocytes. [score:3]
Next, we transfected hADSCs with the miR-125a-3p or miR-483-5p mimic or inhibitor for 72 h and determined the protein levels of RhoA or ERK1/2 by immunoblotting. [score:3]
After 5 weeks of self-differentiation, (A) De novo adipose tissue formation was observed (n = 5); (B) The weights of the de novo adipose tissues were measured (n = 5); (C) The expression levels of miR-125a-3p/5p and miR-483-3p/5p in de novo adipose tissue were detected by real-time PCR (n = 5); (D) The de novo adipose tissue was stained to observe the histology (n = 5); (E) Adipoctye size were analyzed by ImageJ software (F) The protein expression levels of RhoA, ROCK1, total ERK1/2 (T-EKR1/2), and phosphorylated ERK1/2 (T-p-EKR1/2) were analyzed by western blot; and (G) Total nuclear ERK1/2 (n-T-ERK1/2) and p-ERK1/2 (n-p-ERK1/2) were analyzed by western blot. [score:3]
We found that the miR-125a-3p mimic significantly downregulated the luciferase activity of WT-PmiR-RhoA-3′-UTR compared to the control mimic. [score:3]
Different from previous studies, our data showed that miR-125a-3p was highly expressed in the SAT of MSL patients, suggesting that miR-125a-3p may play different roles in MSL adipose tissue. [score:3]
However, the miR-125a-3p mimic apparently decreased the levels of n-T-ERK1/2 and n-p-ERK1/2; while the miR-125a-3p inhibitor increased the levels of n-T-ERK1/2 and n-p-ERK1/2 (Fig. 5B). [score:3]
Conversely, inhibition of miR-125a-3p or miR-483-5p with the corresponding antagomir markedly decreased lipid droplet accumulation (Fig. 2A,B). [score:3]
A recent study has reported that miR-125a-3p is significantly related with fat mass and waist circumstance and that miR-125a-3p expression in the abdominal omental tissue in males is much higher than that in females 39. [score:3]
RhoA and ERK1 are the target genes of miR-125a-3p and miR-483-5p, respectively. [score:3]
How to cite this article: Chen, K. et al. miR-125a-3p and miR-483-5p promote adipogenesis via suppressing the RhoA/ROCK1/ERK1/2 pathway in multiple symmetric lipomatosis. [score:3]
miR-125a-3p agomir significantly promoted adipogenesis, and pCEP4L-ERK1 almost completely inhibited adipogenesis; however, cotransfection group partially restored adipogenesis (Fig. 5E). [score:3]
To further support previous observations 18 27, we designed different mutant site sequences in the 3′-UTR of RhoA and ERK1 and verified the targeting of RhoA and ERK1 by miR-125a-3p and miR-483-5p, respectively. [score:3]
Relative to day 0, approximately 3-4- and 4-6-fold increases of miR-125a-3p and miR-483-5p expression were observed at day 6 and day 12 (Fig. 4A), respectively. [score:3]
The expression of miR-125a-3p and miR-483-5p are increased with the induction of hADSCs. [score:3]
When the cells reached 70–80% confluence, the wild-type (WT) or mutation-type (MT) RhoA and ERK1 3′-UTR plasmids were cotransfected with miR-125a-3p or miR-483-5p mimics (100 nM) or negative control (NC) mimics with Lipofectamine 2000. [score:2]
These results suggested that miR-125a-3p and miR-483-5p might jointly regulate the activity of the RhoA/ROCK1/ERK1/2 signaling pathway. [score:2]
These data further supported the conclusions that miR-125a-3p affects the T-ERK1/2 and p-ERK1/2 levels in the nucleus and that miR-125a-3p and miR-483-5p may jointly regulate the RhoA/ROCK1/ERK1/2 pathway. [score:2]
A proposed mo del of the regulation of adipogenesis by miR-125a-3p and miR-483-5p. [score:2]
miR-125a-3p and miR-483-5p jointly regulate the RhoA/ROCK1/ERK1/2 pathway. [score:2]
Furthermore, cotransfected with the miR-125a-3p agomir and pCEP4L-ERK1 partially restored adipogenesis compared to pCEP4L-ERK1, and similar protein expression of PPARγ and C/EBPα were observed. [score:2]
In summary, we found that both miR-125a-3p and miR-483-5p are significantly increased in the SATs of MSL patients and that miR-125a-3p and miR-483-5p promote adipogenesis through regulating the RhoA/ROCK1/ERK1/2 pathway. [score:2]
miR-125a-3p and miR-483-5p synergistically regulate the RhoA/ROCK1/ERK1/2 pathway. [score:2]
Thus, miR-125a-3p and miR-483-5p regulate the activity of the RhoA/ROCK1/ERK1/2 pathway in vivo. [score:2]
Previous studies have shown that miR-125a-3p and miR-483-5p target RhoA and ERK1, respectively 17 26, which was further supported by our dual-luciferase assay. [score:2]
Our results suggest that miR-125a-3p and miR-483-5p may jointly promote adipogenesis in vivo through regulating the RhoA/ROCK1/ERK1/2 pathway, at least in part. [score:2]
miR-125a-3p and miR-483-5p regulate adipogenesis in hADSCs. [score:2]
miR-125a-3p and miR-483-5p regulate RhoA/ROCK1/ERK1/2 signaling and promote mouse de novo adipogenesis. [score:2]
Similar results were observed in mature adipocytes after hADSCs were transfected with the miR-125a-3p agomir or antagomir for 72 h and induced for 12 days (Fig. 3D). [score:1]
These data suggest that miR-125a-3p and-5p as well as miR-483-3p and-5p may play reverse roles during adipogenesis, at least in adipogenesis of MSL patients. [score:1]
hADSCs were transfected with a lentiviral vector containing pre-miRs of miR-125a (LV-miR-125a), miR-483 (LV-miR-483), or negative control miR (LV-NC) and transplanted to the back subcutaneous tissues of nude mice with the transfected hADSCs or non-tranfected hADSC as control group (Con) or injection of PBS. [score:1]
The de novo adipose tissue formation in LV-miR-125a, LV-miR-483 and cotransfection group were much larger than that of the Con or LV-NC groups, especially in cotransfection group (Fig. 6A,B). [score:1]
Importantly, we found that miR-125a-3p and miR-483-5p promoted de novo adipose tissue formation in nude mice. [score:1]
In addition, adipose tissue staining showed cell size of miR-125a or miR-483 was bigger than Con or LV-NC group, but smaller than cotransfection group (Fig. 6D,E). [score:1]
Next, we transfected hADSCs with miR-125a-3p agomir or pCEP4L-ERK1, or cotransfected with the miR-125a-3p agomir and pCEP4L-ERK1 and induced differentiation for 12 days. [score:1]
LV-miR-125 + 483 further decreased the n-T-ERK1/2 and n-p-ERK1/2 levels. [score:1]
In the LV-miR-125a group, there was no apparent alteration of the T-ERK1/2 and T-p-ERK1/2 levels, but the RhoA and ROCK1 levels were decreased. [score:1]
miR-125a-3p and miR-483-5p significantly promote adipogenesis in hADSCs. [score:1]
Indeed, the miR-125a-3p and miR-483-5p agomir apparently promoted adipogenesis, while their antigomir significantly prevented adipogenesis under either induction or self-differentiation conditions. [score:1]
We found that LV-miR-125a, LV-miR-483, and especially LV-miR-125a in combination with LV-miR-483 significantly increased cells size and promoted de novo fat formation in vivo and de novo adipose tissue weight gain. [score:1]
Interestingly, capsular de novo adipose tissues were found in the LV-miR-125a, LV-miR-483, and cotransfection group; however, no capsular formation was seen in the Con or LV-NC groups. [score:1]
These results demonstrated that miR-125a-3p and miR-483-5p promote adipogenesis in hADSCs. [score:1]
Interestingly, ssc-miR-125a has been found to repress the differentiation of porcine preadipocytes 15. [score:1]
We found that transfection with miR-125a-3p or miR-483-5p significantly promoted lipid droplet accumulation in hADSCs that were induced to mature adipocytes. [score:1]
The hADSCs were transfected with the miR-125a-3p or miR-483-5p agomir, agomir-NC (100 nM), antagomir-NC, or antagomir (200 nM), respectively. [score:1]
To induce de novo adipose tissue, hADSCs were transfected with one of the following lentiviruses: negative control miR (LV-NC), hsa-miR-125a, hsa-miR-483, or hsa-miR-125a +483. [score:1]
In sharp contrast, the miR-125a-3p mimic had no effect on the luciferase activity of MUT-PmiR-RhoA-3′-UTR (Fig. 3A). [score:1]
De novo adipogenesis in vivoTo induce de novo adipose tissue, hADSCs were transfected with one of the following lentiviruses: negative control miR (LV-NC), hsa-miR-125a, hsa-miR-483, or hsa-miR-125a +483. [score:1]
These results imply that miR-125a-3p and miR-483-5p may play an important role in MSL adipogenesis. [score:1]
Our data showed that miR-125a-3p did not affect T-ERK1/2 or T-p-ERK1/2, whereas it apparently altered the levels of n-T-ERK1/2 and n-p-ERK1/2, which was different from other previous studies. [score:1]
miR-125a-3p and miR-483-5p promote de novo adipose tissue formation in nude mice. [score:1]
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[+] score: 191
The mutation site reduced the expression of miR-125a and up-regulate the expression of miR-125a target genes. [score:11]
However, the invasive ability of hESCs transfected with pri-miR-125a normal genotype was significantly lower than that transfected with pri-miR-125a mutant genotype (P<0.01), revealing that pri-miR-125a mutant genotype, i. e. down-regulation of miR-125a, can promote cell invasion via up-regulation of miR-125a target genes. [score:9]
This new mutation site co-exist with the rare alleles of two SNPs, reduces the expression of miR-125a fiercely and alleviates the expression repression of miR-125a target genes. [score:8]
In conclusion, we found one nucleotide mutation co-existed with two SNPs reduced the expression of miR-125a, disturb the expression of miR-125a target genes and enhanced cell invasion ability. [score:8]
Since the function of miRNA mostly depend on repressing the expression of its target genes and one miRNA always have hundreds of targets, so we want to get a clue by using RIP-Chip to identify the changes of “repression profile” in RISC complex in mutant pri-miR-125a genotype group. [score:7]
Meanwhile, cells transfected with pri-miR-125a normal (P<0.01) and mutant genotype (P<0.01) had a higher viability than that transfected with pCR3.1 empty vector, implying that the up-regulation of miR-125a can attenuate mifepristone -mediated the suppression of cell growth. [score:6]
MiR-125a expression level of G-C-A haplotype (the most exist in Chinese women) haplotype is nearly 4 fold higher than A-T-G. Mature miR-125a expressed from A-C-G is nearly 1.6 fold higher than G-C-A haplotype. [score:5]
So here, we suggest that, the reduced expression of miR-125a may induce RPL in mainly three ways: (1) the reduced miR-125a may disturb genes expression in maternal endometrium and misguide the mother to reject normal embryos. [score:5]
To investigate the functional consequences of miR-125a A>G mutation on its target genes, we chose two confirmed miR-125a target genes. [score:4]
In this study, we confirmed a mutation site in 6 RPL patients which co-existed with the rare allele of these two SNP sites and caused a more significant reduction of miR-125a expression. [score:4]
The results indicated that the A>G mutation with two SNPs can affect the expression of ERBB2 by changing the production of miR-125a. [score:4]
To study the function of the mutation site, three haplotypes pri-miR-125a expression plasmids were constructed and transfected into HEK293T cells. [score:4]
As shown in Fig. 4, the proliferation of hESCs was not visibly changed when cells were transfected with normal, mutation pri-miR-125a expression vectors or pCR3.1 plasmid. [score:4]
0114781.g002 Figure 2 (A)The result of northern blot indicates that mutation site co-exist with two SNPs reduce miR-125a expresson. [score:4]
In order to eliminate the background noise of genes expression, we adopted the strategy as follows (Fig. 5C): (1) genes more enriched in mutation group (because of less mir-125a expression) compared with normal genotype should be removed false positive results by intersecting with genes more enriched in mock vector group compared with normal. [score:4]
In order to further explore the possible molecular mechanism that pri-miR-125a mutant genotype induced RPL, RIP-chip assay was used to detect the effect of different pri-miR-125a genotypes on target mRNAs expression profiles on a genome-wide scale. [score:4]
To construct pri-miR-125a expression vectors, fragments (1,016 nt). [score:3]
These data suggest that A>G mutation in pri-miR-125a coding region co-existed with the rare alleles of rs41275794 and rs12976445 contributes to the genetic predisposition to RPL by disordering the production of miR-125a, which consequently meddled in gene regulatory network between mir-125a and mRNA. [score:3]
Different genotype miR-125a expression vector were transfected into HEK293T cells with pRL-TK and pGL3 vector which contained 3′UTR sequence of ERBB2 or LIFR. [score:3]
RIP-chip assay was used to identify the disturbed targets of miR-125a when the site mutation existed. [score:3]
The A>G change decreases miR-125a expression in transfected cells. [score:3]
hESCs were seeded in 96-wells plate and then transfected with different genotypes miR-125a expression vector. [score:3]
ERBB2 is necessary for induction of carcinoma cell invasion 14, so we speculated that pri-miR-125a mutant genotype may enhance cell invasive capacity via increasing the expression of ERBB2. [score:3]
The pCR3.1 -based plasmid, miR-125a mimic and miR-125a inhibitor were transfected by using lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) followed the manufacture’s instruction. [score:3]
However, the cells transfected with pri-miR-125a mutant genotype had lower proliferation capacity than that transfected with pri-miR-125a normal genotype (P<0.05), displaying that the sensitivity of cells to mifepristone -induced the inhibition of cell proliferation was increased by mutant pri-miR-125a. [score:3]
Northern blot was used to detect the expression of mature miR-125a. [score:3]
According to the function of ERBB2, the reduction of miR-125a expression should promote cell proliferation activity. [score:3]
Deleting miR-125a target sites in the 3′-UTR of LIFR or ERBB2 was used as corresponding control. [score:3]
As shown in Fig. 2A, the expression of mature miR-125a was different among these three genotypes. [score:3]
0114781.g004 Figure 4 hESCs were seeded in 96-wells plate and then transfected with different genotypes miR-125a expression vector. [score:3]
These reporter constructs were transiently transfected into HEK293T cells together with an expression plasmid containing alone genotype miR-125a. [score:3]
Impact of nucleotides variants on miR-125a target genes. [score:3]
MiR-125a mimic and miR-125a inhibitor were synthesized by GenePharma Co. [score:3]
The 618 nt 3′-UTR of ERBB2 and a 1043 nt 3′-UTR of LIFR, which contain miR-125a target sites, were PCR-amplified from human genomic DNA and cloned into the downstream of the stop codon of firefly luciferase gene. [score:3]
The A>G Mutation changes the predicted pri-miR-125a secondary structures and enhances their molecular stability. [score:2]
The mutation site in H2 genotype pri-miR-125a cause two apparent changes in loop size and a lower predicted ΔG from −408.50 kcal/mol to −410.60 kcal/mol. [score:2]
In this study, we provide the first piece of evidence that link a new nucleotide mutation of pri-miR-125a to human RPL susceptibility. [score:2]
By gene scanning and functional study, we find a site mutation in pri-miR-125a which cause 204 genes enriched and 139 genes diminished in RISC complex. [score:2]
Functional analysis showed that pri-mir-125a mutant genotype can enhance endometrial stromal cells invasive capacity and increase the sensitivity of cells to mifepristone -induced the inhibition of cell proliferation compared with normal genotype. [score:2]
Two-sample Student’s t-test was used to analyze differentially expressed genes between pri-miR-125a normal and mutant genotypes, and P value <0.05 was considered significant. [score:2]
MiR-125a expression vectors and cell transfection. [score:2]
The genotype distributions of four variants in pri-miR-125a in the complete association samples comprising 389 RPL patients and 652 ethnically matched control individuals were shown in Table 1. The mutation site (Chr19∶52196480, A>G) only existed in 6 patients with heterogeneous pattern and not found in controls and 1000 Genomes data base. [score:2]
0114781.g001 Figure 1 (A) An example of chromatographs showing the heterozygosis on rs41275794 and rs12976445 and the mutation site in pri-miR-125a. [score:2]
The embryo development may also be affected by secretary reduced mother miR-125a. [score:2]
In the previous study, we found one mutation site in pri-miR-125a in two RPL patients in a Chinese-Han population of Beijing (North China). [score:2]
RIP-chip assay to detect the effect of different genotype pri-miR-125a on gene expression profile in cells. [score:2]
Detect mutation site in pri-miR-125a and identify the hyplotypes. [score:2]
Variants in pri-miR-125a and their frequencies. [score:1]
When exposed in mifepristone, pri-miR-125a mutant genotype has a negative influence on cell proliferation ability. [score:1]
So that can explain the negative influence by pri-miR-125a mutant genotype on cellular proliferation mechanisms is independent of ERBB2. [score:1]
The results indicated that there was no significant difference of the effect on hESCs migratory capacity between normal and mutant genotypes pri-miR-125a. [score:1]
location a Alleles b dbSNP Minor allelefrequency Genotypedistribution Con% RPL% p Con RPL p miR-125a Chr. [score:1]
When cells were co -transfected with LIFR and different pri-miR-125a genotypes, the activity of firefly luciferase was not significantly changed in any one group (LIFR and G-C-A, A-C-G or A-T-G genotype; Fig. 2B). [score:1]
The secondary structure of 1016 bp pri-miR-125a sequence was predicted using RNAfold web server (http://rna. [score:1]
Corresponding to pre-miR-125a and its flanking regions (previously determined to have the four genotypes) were amplified from human genomic DNA and cloned into the pCR3.1 vector (Invitrogen, Carlsbad, CA, USA). [score:1]
To further validate our discovery, we collected another population consist of 172 patients and 221 controls from Ningxia (Northwest China) and scanned the same region of pri-miR-125a. [score:1]
After being UV-cross-linked and baked at 80°C for 30 min, the membrane was prehybridized at 42°C for 4 h and then hybridized with 32P-labeled miR-125a or U6 probes at 40°C overnight. [score:1]
This table includes 199 genes enriched in the mutant pri-miR-125a group. [score:1]
So we formulate a hypothesis that there exist some other important mechanisms about the function of miR-125a reduction. [score:1]
Real time PCR used to detect miR-125a quantity in the precipitate. [score:1]
Our previous work indicated that two SNPs in (rs12976445, rs41275794) pri-miR-125a are associated with human RPL. [score:1]
Mutant pri-miR-125a enhances endometrial stromal cells (hESCs) invasive capacity. [score:1]
The firefly activity was a little reduced by the pri-miR-125a A-C-G haplotype, but the difference was not significant (P = 0.36). [score:1]
Mutant pri-miR-125a increases the sensitivity of hESCs to mifepristone. [score:1]
Deleting putative miR-125a binding region in the 3′UTR of ERBB2 (ERBB2-Del) or LIFR (LIFR-Del) was used as corresponding control. [score:1]
Therefore, we treated hESCs with mifepristone to simulate abortion status and further research the effect of pri-miR-125a mutant genotype on cell growth (Fig. 4). [score:1]
The amount of miR-125a in precipitation was tested by using real-time PCR. [score:1]
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Thus, we may hypothesize that a higher down-regulation of miR-125a and a subsequent up-regulation of its targets may cause an activation of anti-oxidant factors, including serum bilirubin. [score:9]
Then, our work is the first study conducted on a large cohort of well-characterized patients with chronic hepatitis C. It demonstrates a marked down-regulation of miR-125a in tumor tissue and a subsequent up-regulation of its oncogenic targets MMP11, SIRT7 and c-Raf. [score:7]
MiR-125a is also down-regulated in other tumors, such as medulloblastoma [30], glioblastoma [31], and lung cancer [32] where it suppresses cell proliferation by targeting Zbtb7a proto-oncogene [33]. [score:7]
This finding is corroborated by in vivo studies showing that miR-125a and -125b are downregulated in ERBB2-amplified and ERBB2 -overexpressing breast cancers [26]. [score:6]
In HCC Hep3B and SNU-449 cells, miR-125a inhibits cell proliferation through the down-regulation of sirtuin-7 (SIRT7), a NAD(+) -dependent deacetylase, and subsequent p21 -dependent cell cycle arrest in G1 [34]. [score:6]
Down-regulation was statistically significant in each group and prominent in HCV patients whose expression of miR-125a was reduced to 45 % (Figure 3). [score:6]
In mammalians, miR-125a appears to be expressed in most tissues, mainly targeting membrane receptors or intracellular signal transductors of mitogenic signals, thus limiting cell proliferation. [score:5]
Expression levels of validated targets of miR-125a in hepatocellular carcinoma. [score:5]
MiR-125a was found to downregulate the truncated isoform of the neurotrophin receptor tropomyosin-related kinase C (t-trkC), with subsequent inhibition of cell proliferation. [score:5]
The expression levels of transcripts targeted by miR-125a were determined by RT-qPCR with iTaq™ Universal SYBR [®] Green Supermix (Bio-Rad). [score:5]
The expression levels of miR-125a and its targeted transcripts were normalized to their respective reference genes by using the 2 [−ΔCt] method. [score:5]
In 2013, Kim JK et al. used microarrays to analyze 16 samples of HCC of unknown etiology and compared the expression of the miRNA with 8 samples on non-matched liver tissue, showing a significant downregulation of miR-125a [34]. [score:5]
The expression levels of validated targets of miR-125a were also determined. [score:5]
With regard to miR-125a, a recent study has shown its downregulation in acute myeloid leukemic cells due to aberrant methylation of a CpG island located 3544 bp upstream of the mature miRNA sequence [56]. [score:4]
In several breast cancer cell lines, miR-125a also targets HuR, an RNA -binding protein that stabilizes transcripts of genes regulating cell proliferation, angiogenesis, rapid inflammatory response and stress response [27]. [score:4]
In the human breast cancer cell line SKBR3, tyrosin kinase receptors ERBB2 and ERBB3 are downregulated by miR-125a leading to diminished cell proliferation and migration [25]. [score:4]
Overall, these data indicate that miR-125a may counteract proliferation and invasion of breast cancer cells through the downregulation of ERBB2, ERBB3, and/or HuR. [score:4]
Based on these data collected in vitro, we measured the expression level of MMP11, Zbtb7a, SIRT7 and c-Raf in tumor biopsies, focusing on those patients showing a downregulation of miR-125a of at least 2-fold. [score:4]
No correlation between the down-regulation of miR-125a and severity of HCC was observed, suggesting that the miRNA is mainly involved in the initiation of the oncogenic process. [score:4]
The correlation between higher serum level of total bilirubin and higher down-regulation of miR-125a is intriguing. [score:4]
Down-regulation of miR-125a in hepatocellular carcinoma. [score:4]
In the same study, we found that c-Raf is a direct target of miR-125a. [score:4]
These conclusions are also supported by the discovery of a germline mutation in the sequence of mature miR-125a that is highly associated with development of breast cancer [28]. [score:3]
This finding is consistent with the observed underexpression of miR-125a in human primary neuroblastomas. [score:3]
Expression of miR-125a in hepatocellular carcinoma biopsies from 55 patients. [score:3]
3) 22 (81.5) -  B 2 (7.1) 3 (11.1) -  C 1 (3.6) 2 (7.4) 0.4 In a recent study, we have evaluated the ability of miR-125a to interfere with the expression of known target genes in hepatocellular carcinoma HepG2 cells. [score:3]
MiR-125a regulates the expression of several genes controlling cell proliferation, migration, and apoptosis [24]. [score:3]
With regard to hepatotropic viruses, miR-125a has been shown to interfere with the expression of hepatitis B virus surface antigen [48– 50] thus limiting viral replication [51]. [score:3]
In HCC, miR-125a is also known to target vascular endothelial growth factor A (VEGF-A), and matrix metalloproteinase-11 (MMP11) [35]. [score:3]
Comparison of the expression levels of miR-125a in hepatocellular carcinoma and non-tumor liver tissue. [score:3]
Otherwise, vectors for the ectopic expression of miRNA mimics [57] may be used to boost the cellular reservoir of miR-125a. [score:3]
Further investigations aimed at the identification of the promoter of the transcription unit of miR-125a will allow the comprehension of the molecular mechanisms governing its expression, eventually leading to treatments to restore its expression in tumor cells. [score:3]
In the case of miR-125a, the antiproliferative activity toward hepatic cells and the antireplicative activity toward HBV are clearly due to inhibition of two different pathways but they may be functionally related. [score:3]
A tumor suppressive role for miR-125a is also supported by a study performed in the human neuroblastoma SK-N-BE cell line [29]. [score:3]
Limited studies on the expression of miR-125a in HCC have also been performed. [score:3]
Correlation between down-regulation of miR-125a in HCC and clinical characteristics. [score:2]
Differences in the mean values were evaluated by the Student's t-test except for the expression levels of miR-125a targets that did not follow a normal distribution and were compared by the Wilcoxon test; the chi-squared test was used to compare categorical variables. [score:2]
MicroRNA-125a expression in HCC from patients with viral or non-alcoholic steatotic hepatitis. [score:2]
In this study, we contributed to the characterization of the tumor suppressive activity of miR-125a by measuring its expression in HCC biopsies and in matched adjacent non-tumor liver tissues and by correlating the obtained data with clinical presentation. [score:1]
One of the aims of the study was to correlate the expression profile of miR-125a-5p in neoplastic and non neoplastic tissue and the clinical characteristics of the subjects enrolled. [score:1]
Since HBV has appeared late in evolution, infecting only mammals and birds, primary role of miR-125a is most likely fine tuning of cell proliferation. [score:1]
It may also be speculated that HBV has become sensitive to miR-125a, among hundreds of other hepatic miRNAs, to coordinate its replication to the host cell proliferation. [score:1]
Sorafenib is the only therapeutic agent for treatment of advanced HCC [20, 21] and a recent study has shown that miR-125a is a downstream effector of the drug in its antiproliferative activity toward carcinoma cells [22]; other microRNAs may also be involved in the mechanism of action of the drug [23]. [score:1]
Evaluation of miR-125a target genes. [score:1]
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Among them, miR-125a inhibits cell proliferation, angiogenesis and cell migration by downregulating the expression of sirtuin-7 [34], vascular endothelial growth factor A, matrix metalloproteinase-11 [35], Zbtb7a [41], and c-RAF [42]. [score:8]
This treatment significantly reduced the expression of TNFAIP3 (Fig.   4C), suggesting the occurrence of a positive self-regulatory loop whereby NF-kB p65 stimulates the transcription of miR-125a, that in turn downregulates TNFAIP3 with further activation of NF-kB pathway, thus strengthening miR-125a transcriptional activation. [score:7]
Its activation by NF-kB, and the ability of miR-125a to downregulate TNFAIP3, provide a link between inflammatory response and miR-125a expression. [score:6]
Bi Q Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGFPLoS One. [score:6]
Nucleotides 371–381 contain methylation sites affecting miR-125a expression in acute myeloid leukemic cells, as shown by the de-methylating agent decitabine, whose cell treatment increased miR-125a expression by more than 10-fold [65]. [score:5]
The authors of the work suggested that early processing by Drosha of SPACA6/miR-125a primary transcript would bypass the splicing of the first intron enhancing the accumulation of the transcription variant 1; otherwise, splicing of the first intron would yield transcription variant 2. We then attempted to validate these results in our experimental system and found that the transfection in HepG2 cells of a vector expressing trans-dominant -negative Drosha (Drosha TN) [51] resulted in a three-fold enrichment of the SPACA6 variant 2 (Fig.   5A), indicating prevailing of the splicing on the primary transcript; on the other hand, the level of miR-125a was reduced, as expected as a consequence of the inhibition of the microprocessor activity (Fig.   5A). [score:5]
Experimental up-regulation of miR-125a by lentivirus -mediated transfection of HCC cells limited cell proliferation and tumor growth in nude mice. [score:4]
Looking for positive regulators of miR-125a expression, we focused our attention on the 3′-end region of 579 segment, since its deletion reduced the promoter activity in both HepG2 and HuH-7 cells. [score:4]
Lin-4/miR-125a plays a fundamental role during development in controlling the expression of Lin-28 protein thus promoting phase transitions and cell differentiation in Nematodes, Insects and Mammals 17– 20. [score:4]
Later, the expression of miR-125a was evaluated, revealing a 2-fold upregulation by p65 (Fig.   4B). [score:4]
Intriguingly, it has been reported that miR-125a constitutively activates the NF-kB pathway by targeting its negative regulator TNFAIP3 in diffuse large B-cell lymphoma [47]. [score:4]
The lower extent of up-regulation of miR-125a compared to the induction of the isolated promoter may be due to post-transcriptional regulation by the RNA -binding protein Lin-28 that limits pre-miR-125a maturation [20]. [score:4]
This is consistent with the previous finding that exposure of macrophages to the fungal pathogen Candida albicans or bacterial lipopolysaccharides up-regulates miR-125a via NF-kB [52]. [score:4]
Finally, the expression levels of miR-125a, SPACA6 and TNFAIP3 were normalized to their respective reference genes by using the 2 [−ΔCt] method and reported as arbitrary units (AU). [score:3]
Svensson D Inhibition of microRNA-125a promotes human endothelial cell proliferation and viability through an antiapoptotic mechanismJ Vasc Res. [score:3]
Expression profiles of miR-125a. [score:3]
These results may also explain the increased expression of miR-125a observed in liver of patients with chronic hepatitis B [50] and shed new light on the observed ability of miR-125a to counteract hepatitis B virus replication 48, 53– 57. [score:3]
Kim SW MicroRNAs miR-125a and miR-125b constitutively activate the NF-κB pathway by targeting the tumor necrosis factor alpha -induced protein 3 (TNFAIP3, A20)Proc Natl Acad Sci USA. [score:3]
These data strongly suggest that the genomic DNA sequence located between -3875 and -3006 bp from pre-miR-99b drives the expression of SPACA6 gene and its intronic miR-99b/let-7e/miR-125a cluster. [score:3]
Although the role of miR-125a during the carcinogenesis is object of extensive research, the mechanisms governing miR-125a expression are still largely unexplored. [score:3]
Taken together, the data suggest the following miRNA expression pathway (Fig.   5B): miR-99b/let-7e/miR-125a are co-transcribed with SPACA6 from the promoter experimentally validated in this work; then, prevailing of splicing produces the SPACA6 transcription variant 2 and represents the first step of miRNA biogenesis and production of SPACA6 protein isoform 2, whereas prevailing of Drosha processing releases the SPACA6 transcription variant 1, leading to production of protein isoform 1. This way, timing of Drosha processing, prior or after splicing, affects pre-mRNA maturation leading to different transcripts and gene products. [score:3]
We then verified the effect of p65 on miR-125a expression in hepatic cells. [score:3]
In this region, de la Rica et al. recently reported the presence of a binding site for p65 subunit of NF-kB whose occupation stimulates miR-125a expression during osteoclast differentiation [46]. [score:3]
Profiling was then extended to cultured human cell lines, revealing an high expression of miR-125a in HepG2, neuroblastoma and lung cancer cells (Fig.   6B). [score:3]
Figure 4Effect of NF-kB on miR-125a expression. [score:3]
Moreover, low tumor expression of miR-125a at time of surgery in HCC patients has been correlated with poor 5-year survival [35]. [score:3]
In this study we showed that miR-125a is wi dely expressed in the adult tissues, were we speculate it may modulate cellular sensitivity to mitogenic signals. [score:3]
MircroRNA-125a-5p (miR-125a), denominated lin-4 in nematodes, is of special interest, since it is very well conserved in evolution [16] and plays a pivotal role in development and cell differentiation 1, 17– 20. [score:2]
Overall, these data suggest that the 579 construct contains most of the regulatory elements responsible for SPACA6/miR-125a transcription. [score:2]
Caygill EE Johnston LA Temporal regulation of metamorphic processes in Drosophila by the let-7 and miR-125 heterochronic microRNAsCurr Biol. [score:2]
It is noteworthy that the isolated 579 bp genomic segment identified as SPACA6/miR-125a promoter is responsive to NF-kB in the luciferase reporter assay as the endogenous gene responds to NF-kB in driving miR-125a expression. [score:2]
MiR-125a expression was analyzed in several murine tissues and resulted to be detectable in all samples, but with some variations. [score:2]
Identification of miR-125a promoter. [score:1]
This effect may be functionally relevant since the pathogenesis of HCC has a common background in chronic inflammation and oxidative stress 48– 50; miR-125a induction by NF-kB may then limit the deleterious consequences of inflammation. [score:1]
Figure 2Nucleotide sequence of miR-125a/SPACA6 promoter. [score:1]
The genomic sequence of miR-125a-5p is located on chromosome 19, in close proximity to those of let-7e and miR-99b (Fig.   1A). [score:1]
We then verified this effect in HCC by transfection of a miR-125a mimic. [score:1]
The nucleotide sequence of the 869 segment with annotation of the putative promoter elements is reported in Fig.   2. Figure 1Isolation of miR-125a promoter. [score:1]
Interplay between SPACA6 pre-mRNA splicing and miR-125a biogenesis. [score:1]
Based on these data, it may be hypothesized that the miR-125a cluster 1) is provided with its own promoter, located within the first intron of SPACA6 gene, or 2) shares with SPACA6 a promoter located upstream of the first exon. [score:1]
As shown in Fig.   1, pre-miR-125a hairpin is located within an intron of the newly assembled SPACA6 transcription variant 2, but its 3′-end is immediately adjacent to the 5′-end of a SPACA6 exon belonging to transcription variant 1. Variant 2 was recently identified with a deep RNA-sequencing approach after blocking the activity of Drosha, thus preventing pri-miRNA processing [45]. [score:1]
With regard to the biogenesis of miR-125a, the collected data indicate that it belongs to an intronic cluster sharing with SPACA6 gene a TATA-less promoter provided with INR and DPE. [score:1]
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These findings suggest that although the IL-4 -mediated regulation of miR-99b and miR-125a expression is STAT6 -dependent, (i) it might not be regulated via direct STAT6 DNA binding or (ii) the regulatory region might be outside of that explored within this study (Fig.   5a). [score:7]
The IL-4 -induced upregulation of miR-342-3p and downregulation of miR-99b and miR-125a-5p proved to be STAT6 -dependent, which was also validated by stem-loop RT-qPCR (Fig.   3c). [score:7]
The IL-4-regulated expression of miR-342-3p, miR-99b, and miR-125a-5p is dependent on IL-4Rα and STAT6 expression as demonstrated by loss of function genetic experiments. [score:6]
miR-125a and miR-125b, containing the same seed sequences, are induced during classical macrophage activation and potentiate M1 polarization through direct inhibition of anti-inflammatory Tnfaip3 (A20) and Irf4 expression [24, 81, 82]. [score:6]
The expression of miR-342-3p was unchanged while miR-193b expression was slightly induced during the monocyte-to-macrophage transition, while both increased significantly in response to IL-4. In contrast, miR-99b and miR-125a-5p showed a significant induction during monocyte–macrophage differentiation. [score:5]
In addition, miR-99b and miR-125a-5p expression were attenuated in IL-4-stimulated macrophages in all four human donors, although the IL-4 -dependent reduction of mir-99b expression did not reach statistical significance (p = 0.056) (Fig.   1c; Additional file 6a). [score:5]
Therefore, we focused our efforts on the identification of the upstream regulator(s) of miR-342-3p, miR-125a, and miR-99b expression during mouse alternative macrophage activation. [score:4]
As shown in Fig.   3b, IL-4 -mediated negative regulation of mature miR-99b and miR-125a-5p expression proved to be Stat6 -dependent in mouse macrophages; hence, it was logical to assume that IL-4 represses the primary miRNA in a similar manner. [score:4]
These results suggest that the conserved IL-4 -dependent regulation of miR-342-3p, miR-99b, and miR-125a-5p expression holds in vivo relevance. [score:4]
Conserved IL-4Rα/STAT6 signaling -dependent regulation of miR-342-3p, miR-99b, and miR-125a-5p expression during in vitro and in vivo mouse alternative macrophage activation. [score:4]
We studied the regulation of miR-342-3p, miR-99b, and miR-125a-5p expression during IL-4 -induced differentiation in vitro in human and murine macrophages as well as in nematode implantation -induced alternatively activated murine macrophages in vivo. [score:4]
Based on this, we determined miR-342-3p, miR-99b, and miR-125a-5p expression in nematode-elicited macrophages at different time points after infection (the experimental design is shown in Additional file 3c). [score:3]
It has been previously described that the common miR-125a/miR-125b target gene Irf4 facilitates M2 macrophage polarization and host response against helminth infection [83, 84]. [score:3]
Furthermore, both miR-99b and miR-125a-5p showed reduced expression during B. malayi -induced alternative macrophage activation, also reinforcing our in vitro findings (Fig.   2b). [score:3]
As expected, we found that both the IL-4 -mediated induction of miR-342-3p as well as the reduction of miR-99b and miR-125a-5p expression were completely abolished in IL-4Rα -deficient macrophages, confirming the requirement of the receptor for transmitting the IL-4 stimulus (Fig.   3a). [score:3]
We found that IL-4 -dependent repression of pri-miR-99b-125a was completely abolished in the absence of Stat6 (Fig.   5c), suggesting that Stat6 is the key transcriptional mediator of the IL-4 -dependent repression of miR-99b and miR-125a-5p expression. [score:3]
c Stem-loop RT-qPCR -based quantification of miR-342-3p, miR-99b, and miR-125a-5p expression in IL-4-stimulated or unstimulated WT and Stat6 KO mouse bone marrow-derived macrophages. [score:3]
Intriguingly, we found that miR-125a expression is reduced during alternative macrophage activation both in vitro and in vivo. [score:3]
Finally, we chose two members of the miR-99b-125a miRNA polycistron, including miR-99b and miR-125a-5p, where IL-4 was able to reduce the dramatic human monocyte–macrophage transition -dependent induction of miRNA expression. [score:3]
b Pri-miR-99b-125a, miR-99b, and miR-125a-5p expression in bone marrow cells (BM), MCSF, and MCSF + IL-4 -treated BMDMs. [score:3]
These data raise the possibility that decreased miR-125a and miR-99b levels might contribute to alternative macrophage activation by leading to increased Irf4 expression. [score:3]
Intriguingly, IL-4 -dependent regulation of miR-342-3p, miR-99b, and miR-125a-5p is conserved between human cells and mouse bone marrow-derived macrophages. [score:2]
These findings collectively suggest a complex role of miR99b, miR-125a, and miR-125b in the regulation of alternative macrophage activation. [score:2]
As shown in Fig.   2a, miR-342-3p, miR-99b, and miR-125a-5p were regulated by IL-4 similar to the human cells. [score:2]
These findings suggest that the IL-4 -mediated regulation of miR-342-3p, miR-99b, and miR-125a-5p is conserved between humans and mice. [score:2]
Similarly to the analyses described above (Fig.   4a), we took advantage of publicly available GRO-seq datesets from unstimulated as well as ChIP-seq datasets from IL-4-stimulated and unstimulated mouse macrophages [65] to identify the primary transcripts coding miR-99b and miR-125a and further investigate the regulation of miR-99b and miR-125a expression. [score:2]
By using IL4Rα- and STAT6 -deficient macrophages, we were able to show that IL-4 -dependent regulation of miR-342-3p, miR-99b, and miR-125a-5p is mediated by the IL-4Rα–STAT6 signaling pathway. [score:2]
We found that three IL-4-responsive miRNAs (miR-342-3p, miR-125a, and miR-99b) showed conserved regulation in both human and mouse alternatively activated macrophages in vitro and in B. malayi nematode-infected mice in vivo. [score:2]
We observed that the majority of IL-4-regulated miRNAs were strictly STAT6 -dependent in mouse macrophages, including miR-342-3p, miR-125a-5p, and miR-99b-5p, as well as the previously studied miR-511-5p and miR-324-5p. [score:2]
In order to determine whether IL-4 represses miR-99b and miR-125a expression at the transcriptional or mRNA maturation level, we measured the expression of both primary (pri-miR-99b-125a) and mature transcripts in mouse bone marrow as well as IL-4-stimulated or unstimulated BMDMs (the genomic localization of the pri-miR-99b-125a-specific primer pair is shown in Additional file 9). [score:2]
miR-99b, miR-125a-5p, and pri-miR-99b-125a expression levels were increased to a similar extent in BMDMs compared with the bone marrow cells (Fig.   5b). [score:2]
a miR-342-3p, miR-99b, and miR-125a-5p expression in IL-4-stimulated or unstimulated wild-type (WT) and IL-4Rα-defficient (IL-4Rα KO) mouse bone marrow-derived macrophages as measured by stem-loop RT-qPCR. [score:1]
We found IL-4 -dependent induction of miR-342-3p and miR-193b and repression of miR-99b and miR-125a-5p. [score:1]
We identified only one overlapping H3K4m3 peak with a divergent GRO-seq signal, a hallmark of an active enhancer, downstream of the miR-99b and miR-125a-coding genomic region, confirming the common TSS and polycistronic transcription of miR-99b and miR-125a (Fig.   5a). [score:1]
b Stem-loop RT-qPCR -based quantification of miR-342-3p, miR-99b, and miR-125a-5p in mouse thioglycolate-elicited and in vivo alternatively activated macrophages. [score:1]
a Stem-loop RT-qPCR -based measurement of miR-342-3p, miR-193b, miR-99b, and miR-125a-5p expression in IL-4-stimulated and unstimulated mouse bone marrow-derived macrophages. [score:1]
IL-4 -dependent induction of miR-342-3p and repression of miR-99b along with miR-125a-5p occurred in both human and murine macrophages in vitro. [score:1]
c Stem-loop RT-qPCR -based measurement of miR-342-3p, miR-193b, miR-99b, and miR-125a-5p expression in human monocytes, 72-h nontreated, and IL-4-stimulated macrophages. [score:1]
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[+] score: 86
In conclusion, we report that miR-125a and miR-125b expression is downregulated in CRC tissues and hypermethylation of miR-125a and miR-125b promoter partially accounts for the reduction of the two miRNAs' expression. [score:8]
In the present study, we showed that miR-125a and miR-125b were frequently downregulated in CRC tissues, which suggested the tumor-suppressive properties of the miR-125 family in CRC. [score:6]
3.1. miR-125 Expressions Are Downregulated in CRC. [score:6]
miR-125a was significantly downregulated in breast and gastric cancer, and miR-125a substantially inhibited the proliferation, migration, and invasion activities of cancer cells [11, 12]. [score:6]
In Figures 1(a) and 1(b), the expression levels of miR-125a and miR-125b were significantly downregulated in CRC tissues compared with nontumor tissues. [score:5]
Hypermethylation of miR-125a and miR-125b promoter was found in CRC, and further analysis showed that the expressions of the two miRNAs were significantly lower in hypermethylated tumor tissues than that in methylated counterparts, suggesting that aberrant CpG methylation in the promoter region of miR-125a and miR-125b might silence its expression in CRC tumorigenesis. [score:5]
The relative expression levels of miR-125a <1.081 were considered as downregulation. [score:5]
Considering the above findings, we wanted to test the expression and methylation status of miR-125 in CRC tissues and adjacent nontumor tissues and then to evaluate whether DNA methylation participates in regulating miR-125 expression in human CRC. [score:4]
The difference of miR-125 promoter methylation status or expression levels between CRC tissues and adjacent normal tissues was examined by Student's t-test. [score:3]
As shown in Figures 3(a) and 3(b), the expression levels of miR-125a and miR-125b were significantly lower in the hypermethylated tumor group than that in the methylated tumor group. [score:3]
The expression levels of miR-125a and miR-125b between the hypermethylated group and methylated group were assessed using Mann-Whitney U test. [score:3]
To date, the expression level of miR-125 in CRC is not clear yet. [score:3]
High expression of miR-125 had been observed in gliomas and prostate cancer [14, 15], while miR-125 levels were demonstrated to decrease in breast and gastric cancer [11, 12]. [score:3]
Depending on cell context, miR-125a and miR-125b function as oncogenes or tumor suppressors. [score:3]
Kim et al. also demonstrated the restoration of miR-125a and miR-125b expression in hepatocellular carcinoma following 5-Aza-dC treatment [19]. [score:3]
The miR-125 family members have been reported to regulate tumor cell proliferation and metastasis. [score:2]
Current studies revealed that the dysregulation of miR-125 occurs in multiple human cancer types [9– 13]. [score:2]
The results showed that the CpG sites were highly methylated in tumor tissues for miR-125a, and the methylation level varied from 8.2% to 96.5%, with a mean ratio of 59.12% in the tumor tissue (Figures 2(b) and 2(c)). [score:1]
Kaplan-Meier analysis showed that miR-125 methylation status was inversely correlated with overall survival of the CRC patients. [score:1]
These findings indicated that hypermethylation of miR-125 family member may be involved in the tumorigenesis of CRC, and it could be a good biomarker for the clinical outcome in CRC patients. [score:1]
The promoters of the two miR-125 family members are both embedded in CpG islands, according to the putative promoter regions. [score:1]
However, the role of miR-125 in CRC is not clear yet. [score:1]
In contrast, the methylation level of miR-125a observed in the adjacent nontumor samples ranged from 0% to 51.8%, with a mean of 19.17% (Figures 2(b) and 2(c)). [score:1]
miR-125a was hypermethylated in 58 (85.3%) of 68 tumors. [score:1]
To determine the prognostic value of miR-125 members for CRC, we analyzed the association between methylation status of miR-125a or miR-125b and survival duration by using the Kaplan-Meier analysis. [score:1]
The relationships of miR-125 methylation status and clinicopathological data were examined by the use of multivariate analysis. [score:1]
Firstly, we measured the expression of miR-125 by using real-time PCR in 68 pairs of tumor and adjacent nontumor tissues. [score:1]
Human miR-125a is located at 19q13, while miR-125b is located at 11q23. [score:1]
The miR-125 family has been reported to be involved in multiple cancers. [score:1]
The family members are present in the mammalian genome: miR-125a localizes to chromosome 19q13, while miR-125b localizes to chromosome 11q23. [score:1]
We designed and validated bisulfate sequencing PCR for the promoter region of miR-125a including 17 CpGs and that of miR-125b including 20 CpGs, respectively (Figure 2(a)). [score:1]
3.2. miR-125a and miR-125b Are Hypermethylated in CRC. [score:1]
Further studies in vitro and in vivo are required to validate the value of miR-125 in CRC tumorigenesis. [score:1]
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[+] score: 84
We found miR-125a to be upregulated in HIV and HIV/MDD, and 15/20 of its dysregulated target genes at the mRNA level to be upregulated (Figure 4). [score:10]
The gene expression in HIV/MDD of genes which are targets of miRNAs that show significant target bias is illustrated in Figure 4. MiR-367 (Accession Number 442912), miR-125a-3p (Accession Number 406910), miR-502-5p (574504), and miR-136 (Accession Number 406927) showed significant target bias across all four windows (asterisks in Figure 3). [score:9]
The gene expression in HIV/MDD of genes which are targets of miRNAs that show significant target bias is illustrated in Figure 4. MiR-367 (Accession Number 442912), miR-125a-3p (Accession Number 406910), miR-502-5p (574504), and miR-136 (Accession Number 406927) showed significant target bias across all four windows (asterisks in Figure 3). [score:9]
A miRNA profile of Alzheimer's Disease patients showed significant overlap with our findings; 11/19 miRNAs found to be dysregulated in the FC in AD [28] were dysregulated in our study in the same direction, including miR125a, miR132, which have CNS developmental roles [14], and were highly significant in our target bias analysis (Figure 3). [score:9]
The direction of the dysregulation of the miRNA is indication by the arrow; for miR-367, miR-136, and miR-125a, the majority of targets are dysregulated in accordance with the miRNAs; while for miR-502, the majority of targets are anticorrelated. [score:8]
0010337.g005 Figure 5 Due to miR-125a's reported involvement in CNS development [26], [27], along with a reported dysregulation in the CSF of Alzheimer's disease [28], we investigated whether a given target of miR-125a would be affected by its overexpression. [score:7]
0010337.g005 Figure 5Due to miR-125a's reported involvement in CNS development [26], [27], along with a reported dysregulation in the CSF of Alzheimer's disease [28], we investigated whether a given target of miR-125a would be affected by its overexpression. [score:7]
0010337.g006 Figure 6 (A) Decreased protein production of IFITM3 in miR-125a overexpressing neuronal cells and (B) decreased secretion of sTNFR-1A in miR-22 overexpressing neuronal cultures. [score:5]
Both miR-125a and miR-22 were found to be upregulated in our analysis of HIV-infected individuals. [score:4]
We used a lentiviral vector system to overexpress either a CDH-GFP control vector, miR-125a, or miR-22 under control of the CMV promoter. [score:3]
We found that IFITM3 protein decreased in response to miR125a overexpression at 3-5 days of post-miR125a induction, Figure 6a. [score:3]
Total protein cell lysates from cells treated exposed to miR-125a were obtained by incubation with a lysis buffer containing 0.15 M NaCl, 5 mM EDTA, 1% Triton X-100, 10 mM Tris-HCl, and 1% SDS with Complete Proteases Inhibitor Cocktail (Roche, Palo Alto, CA). [score:3]
Lentiviral overexpression of (A) miR-22 and (B) miR-125a in primary neuronal cultures. [score:3]
Lentiviral vectors were obtained from Origene (Rockville, MD) which contained human miR-125a (#SC400749) and human miR-22 (#SC400286) mature sequences on a pCMV-MIR backbone. [score:1]
We have therefore provided in vitro evidence that miR-125a can alter protein levels of IFITM3 in primary human neuronal cultures. [score:1]
RNA was isolated on two separate occasions following the miRVana protocol from the frontal cortex tissue and subjected to RT-PCR for miR122 (diamond), miR125a-3p (square), miR132 (triangle), and miR134 (X), and miR495 (asterisk). [score:1]
The following RNAs (Applied Biosystems product ID#s) were analyzed: MammU6 (#4395470), RNU44 (#4373384), miR-122 (#4395356), miR-29a (#4395223), miR-367 (#4373034), miR-142-5p (#4395359), miR-154 (#4373270), miR-214 (#4395417), miR-193a-3p (#4395361), miR-495 (#4381078), miR-125a-3p (#4395310), miR-134 (4373143). [score:1]
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[+] score: 74
These results suggest that miR-125a interacts with the Bmf 3′ UTR to inhibit Bmf expression, and that Sp110 upregulates the expression of Bmf by downregulating miR-125a. [score:13]
Consistently, we found that overexpression of Sp110 significantly downregulated miR-125a in RAW264.7 cells (Fig. 5f), but upregulated Bmf (Fig. 6a). [score:9]
Our data showed that Sp110 upregulated Bmf by inhibiting miR-125a and forced expression of Bmf induces macrophage apoptosis. [score:8]
To confirm that miR-125a-5p suppresses Bmf expression through interaction with the Bmf 3′ UTR, we constructed a miRNA expression vector (pCDH-miR-125a) and Bmf 3′ UTR reporter vectors. [score:7]
RAW264.7 cells were transfected with 50 nM control mimic, miR-125a mimic, control inhibitor or miR-125a inhibitor (Shanghai GenePharma Co. [score:5]
In contrast, transfection of the miR-125a inhibitor enhanced Bmf expression in the RAW264.7 cells (Fig. 6d). [score:5]
Moreover, we found that transfection of RAW264.7 cells with the miR-125a mimic inhibited endogenous expression of Bmf. [score:5]
We also noted that expression of miR-99b, miR-125a and miR-21a was inhibited by Sp110 (Fig. 5f). [score:5]
Our integrative analysis of Sp110-regulated mRNA and miRNA data revealed that the apoptosis-inducing gene, Bmf 26, is a potential target of miR-125a. [score:4]
Targetscan database prediction showed that the 3′ UTR of Bmf mRNA consists of two conserved miR-125a-5p binding sites (Fig. 6b). [score:3]
Of note, in both uninfected and Mtb-infected macrophages, Sp110 induced miR-155, miR-342, miR-3470a and miR-532, but inhibited let-7e, miR-1249, miR-125a, miR-132, miR-152, miR-16-1, miR-182, miR-183, miR-23a, miR-28a, miR-5114, miR-99a and miR-99b. [score:3]
The luciferase assay results showed that overexpression of miR-125a significantly decreased the luciferase activity of the wild-type Bmf 3′ UTR reporter; however, the two binding sites in the mutated reporter vector did not respond to the increased level of miR-125a (Fig. 6c). [score:2]
HEK293T cells were cotransfected with pCDH-miR-125a and a wild-type or mutated Bmf 3′ UTR reporter vector. [score:1]
Furthermore, the RAW-Control and RAW-Sp110 cells were transfected with the miR-125a mimic, and the immunoblot result showed that the miR-125a mimic decreased the Bmf protein level in both RAW-Control and RAW-Sp110 cells (Fig. 6e). [score:1]
Briefly, HEK293T cells were cotransfected with luciferase reporter and pCDH-miR-125a using Lipofectamine 2000 Reagent (Invitrogen, Carlsbad, CA). [score:1]
To construct the pCDH-miR-125a vector, DNA sequence of the primary miR-125a was amplified and inserted into the pCDH-CMV-MCS-EF1-copGFP vector (System Biosciences). [score:1]
Moreover, we found that Sp110 -mediated apoptosis decreased in Mtb-infected macrophages transfected with the miR-125a mimic (Fig. 6i,j). [score:1]
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[+] score: 65
We analyzed the expression of each of the six putative target genes after having modified the expression of each of the respective microRNAs; again, a miRNA mimic for miR-29b, miR-205, or miR-221 was transfected into cells to mimic miRNA overexpression; separately, an anti-miR-125a-5p oligonucleotide was transfected into cells to inhibit miR-125a-5p activity. [score:11]
Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to. [score:8]
However, miR-125a-5p expression is significantly upregulated in lung squamous cell carcinoma relative to that in normal lung tissue [28] and miR-125a-5p expression was associated with enhanced the pathological stage and lymph node metastasis in non-small cell lung cancer [29]. [score:8]
Ectopic overexpression of miR-29b (A), miR-205 (B), or miR-221 (C) via transfection of a corresponding miRNA mimic and downregulation of miR-125a-5p (D) via transfection of an anti miRNA oligonucleotide made HuH28 cells more sensitive to Gem. [score:6]
0077623.g004 Figure 4 Ectopic overexpression of miR-29b (A), miR-205 (B), or miR-221 (C) via transfection of a corresponding miRNA mimic and downregulation of miR-125a-5p (D) via transfection of an anti miRNA oligonucleotide made HuH28 cells more sensitive to Gem. [score:6]
Our results indicated that expression levels of miR-29b, miR-125a-5p, miR-205, and miR-221 may be useful as diagnostic markers of sensitivity to, and that PIK3R1 and MMP-2 could become molecular targets of anti-tumor therapies for patients with CCA. [score:5]
Our computer -based analysis identified that the target of miR-125a-5p was DUSP6, which is an anti-oncogene; however, DUSP6 expression was not enhanced by transfection of the anti-miR-125a-5p oligonucleotide. [score:5]
miR-125a-5p was regarded as a representative onco-miRNA in the CCA cells, and ectopic selective downregulation of miR-125a-5p repressed CCA cell proliferation. [score:4]
Transfection of a mimic of miR-29b, miR-205, or miR-221 or inhibition of miR-125a-5p via a complementary oligonucleotide significantly restored Gem sensitivity to HuH28 cells near clinical therapeutic concentration, 1×10 [−4] M (Figure 4). [score:3]
Our findings indicated that oligonucleotide -mediated selective suppression of miR-125a-5p strongly reduced CCA cell viability. [score:3]
Dual specificity phosphatase 6 (DUSP6) was predicted to be the putative anti-oncogene target of miR-125a-5p (Figure 5). [score:3]
Reportedly, miR-125a-5p is an anti-onco miRNA in HCC and gastric cancer [26], [27]. [score:1]
The genes encoding the precursors to miR-125a-5p, miR-99b and let7e are located in a conserved gene cluster on Chromosome 19 in humans. [score:1]
The p values between miR-29b, miR-205 and miR-221 mimic transfection versus non-silencing miRNA mimic (relative cell viability was 82 ± 4 % at 1×10 [−4] M Gem) and anti-miR-125a-5p oligonucleotide transfection versus negative control oligonucleotide (relative cell viability at 1×10 [−4] M Gem was 70 ± 6 %) were smaller than 0.001. [score:1]
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[+] score: 59
microRNAs downregulated in quiescent cells included miR-18, miR-20, miR-29, and miR-7, and microRNAs upregulated with quiescence included let-7b, miR-125a, miR-30, miR-181, miR-26, and miR-199. [score:7]
During differentiation or quiescence, let-7 and miR-125 may actively suppress the expression of cell cycle -associated transcripts through a post-transcriptional mechanism that reinforces the out-of-cycle state established by transcriptional mechanisms. [score:5]
Possible candidates for these transcripts include previously reported cell cycle targets of let-7 such as RAS [39], CCND1 [90], CDC25 [35], and CDC34 [36], and miR-125 targets such as BCL3 [91] and ETS1 [92]. [score:5]
We also found that let-7 and miR-125 were upregulated in quiescent cells. [score:4]
Although miR-125 and let-7 are co-conserved and co-regulated in many organisms, the two microRNAs also share some overlapping target genes [33, 93, 94], which suggests the possibility that some of the functional effects on the cell cycle exerted by each microRNA are redundant. [score:4]
Our results indicate that in reversibly arrested cells, miR-125 and let-7 downregulate cell proliferation-promoting genes. [score:4]
To assess whether let-7 and miR-125 have complementary effects on cell cycle progression, we overexpressed a combination of the two microRNAs. [score:3]
Proliferating or 4-day serum-starved primary fibroblasts were reverse -transfected using Oligofectamine (Life Technologies) with a 50 nM final concentration of Pre-miR microRNA duplexes let-7b, miR-125a, miR-29a, a 1:1 combination of let-7b and miR-125a, or the Negative Control #2 non -targeting control (Life Technologies). [score:3]
Because both let-7 and miR-125 are upregulated in quiescence, we investigated whether let-7 and miR-125 have complementary roles in cell cycle regulation. [score:3]
Here we show that, when overexpressed, both miR-125 and let-7 specifically affect the ability of quiescent fibroblasts to re-enter the proliferative cell cycle from quiescence induced by serum starvation. [score:3]
Overexpression of let-7 and miR-125 together resulted in a further accumulation of cells in G [0]/G [1 ]and even slower S phase entry than either individually (Figure 4A, P = 1. [score:3]
In many organisms, lin-4 (miR-125) and let-7 are both important for developmental programs involving differentiation or cell cycle arrest [26, 31]. [score:2]
The complementarity of let-7 and miR-125In many organisms, lin-4 (miR-125) and let-7 are both important for developmental programs involving differentiation or cell cycle arrest [26, 31]. [score:2]
Our data indicate that administration of miR-125 or a combination of let-7 and miR-125 might have even greater effects. [score:1]
In C. elegens, the lin-4 microRNA (miR-125 in mammals) acts in the same heterochronic pathway of temporal differentiation as let-7 [27]. [score:1]
let-7 and miR-125 non-redundantly delay cell cycle entry from quiescence. [score:1]
let-7 and miR-125 non-redundantly delay cell cycle entry from quiescence let-7 plays roles in differentiation, cancer, and the cell cycle, as discussed above. [score:1]
We observed an even stronger effect on cell cycle re-entry with miR-125 than for let-7. At 20 and 24 h after transfection, cells transfected with miR-125 contained more cells in G [0]/G [1 ]and fewer cells in S phase than controls (Figure 4A, P = 7. [score:1]
Upon restimulation, these genes are released from let-7 and miR-125 -mediated repression and are required for normal cell cycle re-entry. [score:1]
Our data and the literature, taken together, support a mo del in which miR-125 and let-7 family members are induced upon the commitment to a cell state lineage or reversible cell cycle exit. [score:1]
The complementarity of let-7 and miR-125. [score:1]
In vertebrates, mature let-7 and miR-125 are largely absent from early embryos and are induced upon differentiation [84- 86]. [score:1]
We monitored the functional roles of let-7 and miR-125 on cell cycle re-entry from quiescence using the same method we used for miR-29 as described above. [score:1]
Figure 4Cell cycle and cell size effects of microRNAs let-7, miR-125, and miR-29. [score:1]
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[+] score: 57
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-19a, hsa-mir-20a, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-30a, hsa-mir-33a, hsa-mir-96, hsa-mir-98, hsa-mir-103a-2, hsa-mir-103a-1, mmu-let-7g, mmu-let-7i, mmu-mir-23b, mmu-mir-30a, mmu-mir-30b, mmu-mir-99b, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-146a, mmu-mir-155, mmu-mir-182, mmu-mir-183, mmu-mir-24-1, mmu-mir-191, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-181b-1, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-221, hsa-mir-223, hsa-mir-200b, mmu-mir-299a, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-23b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-146a, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-20a, mmu-mir-21a, mmu-mir-23a, mmu-mir-24-2, mmu-mir-26a-1, mmu-mir-96, mmu-mir-98, mmu-mir-103-1, mmu-mir-103-2, mmu-mir-148b, mmu-mir-351, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, mmu-mir-19a, mmu-mir-25, mmu-mir-200c, mmu-mir-223, mmu-mir-26a-2, mmu-mir-221, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-181b-1, mmu-mir-125b-1, hsa-mir-30c-1, hsa-mir-299, hsa-mir-99b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-361, mmu-mir-361, hsa-mir-365a, mmu-mir-365-1, hsa-mir-365b, hsa-mir-375, mmu-mir-375, hsa-mir-148b, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, mmu-mir-433, hsa-mir-429, mmu-mir-429, mmu-mir-365-2, hsa-mir-433, hsa-mir-490, hsa-mir-193b, hsa-mir-92b, mmu-mir-490, mmu-mir-193b, mmu-mir-92b, hsa-mir-103b-1, hsa-mir-103b-2, mmu-mir-299b, mmu-mir-133c, mmu-let-7j, mmu-mir-30f, mmu-let-7k, mmu-mir-9b-2, mmu-mir-9b-1, mmu-mir-9b-3
The reduction of Cxcr3, Fut1, and Rhobtb1 expression was associated with an increased expression of miR-148b, miR-125a, and miR-182, which target Cxcr3, Fut1, and Rhobtb1 mRNAs, respectively, suggesting that, in addition to Aicda and Prdm1, which are already downregulated by HDI, other genes can also be downregulated by HDI through upregulation of their targeting miRNAs. [score:18]
In addition to the targeting sites for miR-155, miR-181b, and miR-361, the 3′ UTR of mouse Aicda mRNA also contains the putative target sites for miR-125a, miR-351, miR-92b, miR-26a, and miR-103 (identified by using miRNA -targeting prediction tools: TargetScan. [score:9]
In addition to miR-23b, miR-30a, and miR-125b, which, as we showed by qRT-PCR and miRNA-Seq, are upregulated by HDI, several other putative Prdm1 targeting miRNAs, including miR-125a, miR-96, miR-351, miR-30c, miR-182, miR-23a, miR-200b, miR-200c, miR-365, let-7, miR-98, and miR-133, were also significantly increased by HDI. [score:6]
Figure 8The Prdm1 targeting miRNAs miR-23b, miR-125a, miR-351, miR-30a/c/d, miR-182, miR-96, miR-98, miR-200b/c, and miR-365 are upregulated by HDI. [score:6]
In the presence of HDI, miR-125a expression was increased by up to 7.5-fold, perhaps suggesting a more important role of this miRNA than miR-125b in modulating Blimp1 expression. [score:5]
miR-125a and miR-351 contain the same seed sequence as miR-125b, and therefore potentially target Prdm1 3′ UTR at the same site as miR-125b. [score:3]
org), we identified miR-125a, miR-125b, miR-96, miR-351, miR-30, miR-182, miR-23a, miR-23b, miR-200b, miR-200c, miR-33a, miR-365, let-7, miR-98, miR-24, miR-9, miR-223, and miR-133 as PRDM1/Prdm1 targeting miRNAs in both the human and the mouse. [score:3]
Like miR-125b, miR-125a also potentially targets Prdm1 in both human being and mouse, as predicted by the sequences (Figure 8). [score:3]
miR-125 is a an evolutionarily conserved miRNA family consisting of three paralogs, including miR-125a, miR-125b-1, and miR-125b-2 (miR-125b). [score:1]
The abundance of miR-125a in B cells induced to undergo CSR and plasma cell differentiation by LPS plus IL-4 was much greater than that of miR-125b, as in all three experiments. [score:1]
Recent studies have presented strong evidence for a role of the miR-125 family in the immune response. [score:1]
miR-125a shares the same seed sequence with miR-125b. [score:1]
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[+] score: 56
Aberrant expression of miR-125a-3p has been documented in serum of patients with pancreatic cancer, biliary-tract cancer, systemic lupus erythematosus, and moyamoya disease 28– 30. [score:5]
miR-125 family, a highly conserved miRNA family throughout evolution, is consist of miRNA-125a-3p, miR-125a-5p, miR-125b-1 and miR-125b-2. The aberrant expression of miR-125 family is tightly related to tumorigenesis and tumor development[13]. [score:4]
In addition to the location, we also found significant correlation of up-regulation of miR-125a-3p with non-tumor infiltration, whereas CEA is associated with tumor size, infiltration depth, and differentiation degree, which is consistent with results from recent study [2]. [score:4]
MiR-125a-3p expression reduced migration and increased apoptosis of prostate cancer cells by targeting Fyn, FAK and paxillin 31, 32. [score:4]
These results indicate that expression of miR-125a-3p is independent from CEA and miR-125a-3p may play critical roles when CRC invades the peripheral nerves. [score:3]
These evidences collectively indicated miR-125a-3p may play its multiple roles as tumor inhibitor. [score:3]
Serum level of CEA and the expression level of miR-320c and miR-125a-5p were respectively stratified into high and low group with their geometric mean as cut-off. [score:3]
After normalization to miR-30e-5p, examination of the relationship between the early stage colon cancer and each marker demonstrated a statistically significant up-regulation of miR-125-3p (Fig.   2A, P = 0.018) and miR-320c (Fig.   2B, P = 0.028) in colon cancer patients when compared to healthy controls. [score:3]
Relative expression levels of miR-125a-3p (A) and miR-320c (B) in the CRC patients (Case) and healthy controls (Control) are shown. [score:3]
Significant synergistic effect was found when the up regulation of miR-125a-3p was combined with CEA level, which generated an AUC of 0.8552 (Fig.   3D, P < 0.0001). [score:2]
In addition to direct action on tumorigenesis, miR-125a-3p was found to increase chemosensitivity of breast cancer cell by 3′-UTR of BRCA1 [35]. [score:2]
By combining with CEA and miR-125a-3p, our multivariant mo del shows an increased diagnostic power with AUC = 0.855. [score:1]
MiR-125-3p and miRNA-320c can distinguish early-stage colon cancer from the healthy controls. [score:1]
MiR-9-1, miR-320d, miR-125-3p, and miR-320c were the only four miRNAs that could be stably amplified. [score:1]
Shown are statistically analysis on trend between miR-125a-3p versus tumor location and nerve infiltration (A), and miR-320c versus tumor location and nerve infiltration (B). [score:1]
A study showed that PI3K/AKT/mTOR pathway is involved in miR-125a-3p induced reduction of the migration and invasion of liver cancer [34]. [score:1]
As shown in Table  3 and Fig.   3, the performance of miR-125a-3p yielded area under the ROC curve (AUC) values of 0.6849 (Fig.   3A, P < 0.001) and miR-320c with AUC = 0.5982 (Fig.   3B, P = 0.1459), in comparison to CEA with AUC = 0.8362 (Fig.   3C, P < 0.0001). [score:1]
Using miR-30e-5p as endogenous normalizer, we found that level of exosomal miR-125a-3p significantly elevated in patients with early stage CRC (p = 0.0074). [score:1]
Functional role of miR-125a-3p in the process of CRC remains to be fully elucidated. [score:1]
In this follow up study, we selected nine miRNA candidates (miR-125-3p, miR-320c, miR-320d, miR-9-1, miR-139, miR-125a-5p, miR-4792, miR-376, miR-543, miRNA-381) for validation in the independently recruited patients with early-stage (I, II) colon cancer. [score:1]
In this study, we selected miR-9-1, miR-125a-3p, miR-125a-5p, miR-320c, miR-4792, miR-376, miR-543, and miR-381 as diagnostic candidates for validation. [score:1]
Our follow-up study confirmed one miRNA candidate (miR-125a-3p) with potential for screening patients with early-stage CRC when combining with other diagnostic test. [score:1]
With further optimization, the plasma exosomal miR-125a-3p may provide additional option to distinguish the early-stage CRC from healthy controls. [score:1]
The performance of miR-30c (A), miR-125a-3p (B), CEA (C), and miR-125a-3p plus CEA (D) yielded area under the ROC curve (AUC) values of 0.5982 (P < 0.1459), 0.6849 (P = 0.0156), 0.8362 (P < 0.0001), and 0.8552 (P < 0.0001). [score:1]
MiR-9-1, miR-125a-3p, miR-125a-5p, miR-320c, miR-320d, miR-4792, miR-376, miR-139, miR-543, and miR-381(MS00010752, MS00008554, MS00003423, MS00041867, MS00031710, MS00045087, MS00007392, MS00003493, MS00010080, MS00004116, QIAGEN, Valencia, CA) were selected for downstream validation. [score:1]
Correlation analysis showed that miR-125a-3p and miR-320c were not correlated with tumor size, infiltration depth, and differentiation status (Tables  4 and S1). [score:1]
Among the selected miRNAs, miR-125a-5p was barely detectable, consistent with its relative low copy in the RNA sequencing dataset. [score:1]
We showed that there was a trend that miR-125a-3p is higher in patient with left CRC than those with right CRC. [score:1]
As shown in Table  4 and Fig.   4A, miR-125a-3p demonstrated a borderline statistical significance to be up regulated in the left colon cancer when compared to the right (P = 0.0553). [score:1]
In lung cancer, miR-125a-3p induces apoptosis of cancer cell via p53 dependent and p53 independent ways [33]. [score:1]
Our results suggest that the best predictive mo del was the combination of miR-125a-3p and CEA. [score:1]
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In particular, it has been shown that hsa-miR-125a-5p, a miRNA expressed in the human liver (12), is able to target a viral sequence within the overlapping polymerase and surface antigen coding regions (13), inhibiting the expression of HBsAg in vitro. [score:9]
A more recent study by Li et al. (30) demonstrated an upregulation of this miRNA in a murine mo del of carbon tetrachloride -induced liver fibrosis; furthermore, they showed how the downregulation of miR-125a-5p could prevent the activation of hepatic stellate cells in vitro. [score:7]
In 2012, Park et al. (29) showed that TGF-β, a profibrogenic cytokine, could induce an upregulation of hsa-miR-125a-5p in HBV transfected hepatocytes. [score:4]
miR-125a-5p is present in all animals with bilateral symmetry; in mammalians, it is expressed in most tissues (23) where negatively regulates cell proliferation (24). [score:4]
To confirm the association between liver hsa-miR-125a-5p and the presence of an advanced liver disease and to avoid a possible confounding effect of other factors such as age and the plasma HBV-DNA level, a multivariate logistic regression analysis was performed. [score:3]
This study demonstrates a correlation between the tissue expression of hsa-miR-125a-5p and the progression of liver damage in a group of patients with occult or overt HBV infection. [score:3]
Figure 1 miR-125a-5p expression according to liver fibrosis. [score:3]
This study suggests a correlation between the tissue expression of hsa-miR-125a-5p and the progression of liver damage in a group of patients with occult or overt HBV infection. [score:3]
In this study, we aimed to correlate the hepatic expression pattern of hsa-miR-125a-5p with the concentrations of HBV-DNA in liver tissue and the progression of fibrosis in patients with overt or occult HBV infection. [score:3]
In this study, on a larger HBV population, 64 consecutive patients with overt and 10 with occult HBV infection were enrolled and the expression levels of liver hsa-miR-125a-5p were determined, along with clinical, biochemical, and histological parameters. [score:3]
However, the multivariate analysis that identified the miRNA concentrations as independent predictor of advanced liver damage (regardless of the viral load) suggest a role of miR-125a-5p in the process of fibrogenesis, not correlated to the inhibitory effect on HBV replication. [score:3]
If confirmed, these data suggest the hsa-miR-125a-5p may be a novel biomarker of hepatic damage. [score:1]
This is may be due to the inclusion in this study of patients with advanced stages of fibrosis, not included in our previous study, infection by different HBV strains inducing a lower miR-125a expression response (all patients in the former study were infected with a genotype D, while five patients in this paper have a genotype E and two a genotype A), or different serological characteristics (e. g., HBeAg -positive patients, not included previously). [score:1]
The 10 patients in occult HBV group, all cirrhotic, showed a high liver concentrations of miR-125a-5p (median, IQR: 5.47, 2.43 AU). [score:1]
In fact, the liver has-miR-125a-5p concentrations were higher in the patients with higher fibrosis score. [score:1]
To evaluate the correlation between the hepatic expression pattern of hsa-miR-125a-5p and HBV-DNA and the progression of fibrosis in patients with overt or occult HBV infection. [score:1]
Quantitation of HBV DNA and miR-125a in Tissue Samples. [score:1]
The same group demonstrated a strong correlation between serum concentrations of miR-125a-5p and staging of fibrosis in 91 patients with CHB (31). [score:1]
Tissue concentrations of HBV-DNA and hsa-miR-125a-5p were then analyzed by real-time quantitative PCR. [score:1]
Moreover, the lack of control groups with different etiologies and virological characteristics makes it difficult to understand the real correlation between the miR-125a expression and the liver fibrosis. [score:1]
Multivariate analysis identified liver hsa-miR-125a-5p as an independent predictor of fibrosis >5 (OR: 2.08, CI 95%: 1.11–3.85, p = 0.02) (Table 3). [score:1]
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Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-29a, hsa-mir-31, hsa-mir-99a, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-30c-2, hsa-mir-147a, hsa-mir-10a, hsa-mir-34a, hsa-mir-181b-1, hsa-mir-199a-2, hsa-mir-203a, hsa-mir-204, hsa-mir-217, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-200b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-125b-1, hsa-mir-132, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-125b-2, hsa-mir-126, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-193a, hsa-mir-195, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, hsa-mir-30c-1, hsa-mir-219a-2, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-302d, hsa-mir-374a, hsa-mir-375, hsa-mir-378a, hsa-mir-330, hsa-mir-328, hsa-mir-342, hsa-mir-325, hsa-mir-424, hsa-mir-429, hsa-mir-450a-1, hsa-mir-486-1, hsa-mir-146b, hsa-mir-497, hsa-mir-520e, hsa-mir-520f, hsa-mir-520a, hsa-mir-520b, hsa-mir-520c, hsa-mir-520d, hsa-mir-520g, hsa-mir-520h, hsa-mir-450a-2, hsa-mir-503, hsa-mir-608, hsa-mir-625, hsa-mir-629, hsa-mir-663a, hsa-mir-1271, hsa-mir-769, hsa-mir-378d-2, hsa-mir-675, hsa-mir-147b, hsa-mir-374b, hsa-mir-663b, hsa-mir-378b, hsa-mir-378c, hsa-mir-374c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-4661, hsa-mir-219b, hsa-mir-203b, hsa-mir-378j, hsa-mir-486-2
Thus, it is suggested that the overexpression of miR-125a can inhibit the levels of RANTES by controlling the expression of its target gene KFL13 [58]. [score:9]
When miR-125a is overexpressed in T cells, there is a reduction in the expression of KFL13 and the chemokine RANTES (regulated on activation, normal T-cell expressed and secreted), or also known as CCL5. [score:8]
It observed a lower expression of miR-125 in SLE patients as compared to controls and an increased expression of its target Kruppel-like factor 13 (KFL13). [score:6]
It seems that miR-125a is important in the regulation of T cell functions by suppressing the expression of effector T cell factors [59, 60]. [score:6]
As a result, the authors suggested an anti-inflammatory action of these PUFAs in the inflammatory milieu that was mediated by the downregulation of miR-146a, miR-146b, miR-21, miR-125a, and miR-155, which are related to the pro-inflammatory response that is triggered by NF-kB signaling [106]. [score:4]
Among these, miR-328, miR-330-3p, miR-221, and miR-125a-5p had their expressions reduced, while miR-192, miR-486-5p, miR-19b, miR-106a, miR-130b, miR-18a, and miR-769-5p displayed increased levels after the intervention. [score:3]
Blood samples of patients with systemic lupus erythematosus (SLE) and normal controls were collected and PBMCs were isolated for miR-125a expression analyses. [score:3]
Pan W. Zhu S. Dai D. Liu Z. Li D. Li B. Gagliani N. Zheng Y. Tang Y. Weirauch M. T. Weirauch MT: MiR-125a targets effector programs to stabilize Treg -mediated immune homeostasisNat. [score:2]
Zhao X. Tang Y. Qu B. Cui H. Wang S. Wang L. Luo X. Huang X. Li J. Chen S. MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosusArthritis Rheumatol. [score:2]
Lee H. -M. Kim T. S. Jo E. -K. MiR-146 and miR-125 in the regulation of innate immunity and inflammationBMB Rep. [score:2]
The miR-125 family has been associated with immune responses [57]. [score:1]
Sun Y. -M. Lin K. -Y. Chen Y. -Q. Diverse functions of miR-125 family in different cell contextsJ. [score:1]
At 30 min after digestion, 64% of miR-223 was degraded, while 23% of miR-125 was degraded, demonstrating the distinct digestion kinetics of these two miRs. [score:1]
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The miR-125a and miR-125b function as tumor suppressors in SKBR3 cells, a HER2 -overexpressing human breast cancer cell line, by suppressing HER2 mRNA and protein levels. [score:7]
These results suggest that miR-125a can potentially aid in tumor suppression in breast cancer by utilizing HuR as a direct and functional target. [score:6]
Further research showed that miR-125a and miR-125b are both downregulated in HER2 -overexpressing breast cancers [53]. [score:6]
Since miR-335 and miR-125 are both downregulated across numerous highly metastatic cell lines and exhibit abilities to suppress metastasis of breast cancer cells, further exploration of either miRNA would be beneficial for breast cancer therapeutics research. [score:6]
The miR-125a represses translation of HuR through a target site in the 3′ UTR. [score:5]
Overexpressing miR-125a led to decreased HuR protein levels, suppressed cell growth, and reduced cell migration and proliferation. [score:5]
The miR-125a and miR-125b were both found to be significantly downregulated in breast cancer patients. [score:4]
Altered expression of miR-125 has been observed in several malignancies, including breast cancer [49, 50]. [score:3]
Their work [51] showed that miRNA-125a is inversely correlated with HuR expression in various breast carcinoma cell lines. [score:3]
The miR-125 has two known isoforms in humans: miR-125a and miR-125b. [score:1]
Guo et al. [51] explored the role of miRNA-125 in breast cancer after observing [22, 52] that there were decreased levels of miRNA-125 in breast tumors in comparison to normal breast tissues. [score:1]
3.2. miRNA-125. [score:1]
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The highly expressed aae-miRNA-125 and aae-miR-100 were both upregulated in CHIKV-infected Ae. [score:6]
The highly expressed miRNAs, aae-mir-bantam, aae-mir-263a, aae-mir-125 and aae-mir-285 were upregulated in CHIKV-infected Ae. [score:6]
MicroRNA inhibitors were designed based on the sequences of the following select microRNAs, aae-mir-12, aae-mir-125, aae-mir184, aar-mir-375, aae-mir-2490 and a control inhibitor with random sequence, Scramble, that was designed based on a previous study [30]. [score:5]
MicroRNA-125, a homolog of Drosophila miR-let-7, is expressed in specific developmental stages of Drosophila [53]. [score:4]
albopictus saliva whereas aae-mir-125 (2.2-fold), aae-mir-263a (3.4-fold), aae-mir-184 (1.3-fold) and aae-mir-100 (2.0-fold) were all upregulated in comparison with uninfected Ae. [score:4]
Mosquito (AAG-2 and C6/36) and mammalian (BHK-21) cells were transfected with miRNA inhibitors, a) MIR-12, b) MIR-125, c) MIR-184, d) MIR-375 and e) MIR-2940, and then infected with CHIKV at 72 hours post-transfection. [score:3]
All miRNA inhibitors (MIR-12, MIR-125, MIR-184, MIR375 and MIR-2490) were synthesized by Integrated DNA Technologies [©]. [score:3]
Target sites for mir-125a and mir-125b have been predicted to be within the 3′UTR of both mouse and human TNF-α transcripts [57] and miR-125b levels either increase or decrease in response to TNF-α stimulated macrophages both in vitro and in vivo [57]. [score:3]
0003386.g002 Figure 2 Mosquito (AAG-2 and C6/36) and mammalian (BHK-21) cells were transfected with miRNA inhibitors, a) MIR-12, b) MIR-125, c) MIR-184, d) MIR-375 and e) MIR-2940, and then infected with CHIKV at 72 hours post-transfection. [score:3]
Therefore, both aae-mir-125 and aae-mir-100 could be contributing to regulating immune cell activity at the bite site in order to influence CHIKV replication. [score:2]
albopictus saliva were from aae-mir-125 (4333), aae-mir-263a (4293), aae-mir-8 (2609), aae-mir-184 (2332) and aae-mir-100 (2255) (Table 3). [score:1]
aegypti saliva were aae-mir-8 (50004), aae-mir-2940 (21514), aae-mir-263a (20584), aae-mir-bantam (18002), aae-mir-125 (15735), aae-mir-100 (13160), aae-mir-14 (12958) and aae-mir-285 (10006) (Table 1). [score:1]
aegypti saliva and these include aae-mir-8, aae-mir-2940, aae-mir-263a, aae-mir-bantam, aae-mir-125, aae-mir-184, aae-mir-281and aae-mir-100 all of which have been identified in Aedes spp. [score:1]
MicroRNA-125, miR-100 and miR-let-7 are part of the same primary transcript and originate from a common genomic locus in Drosophila [54]. [score:1]
AAG-2 cells: At 24- 48 h. p. i., CHIKV titers were significantly lower (p < 0.05) in cells transfected with MIR-12 (Fig. 2A), MIR-125 (Fig. 2B) and mir-2490 (Fig. 2E) than in Scramble cells. [score:1]
CHIKV titers peaked at 72 h. p. i. in AAG-2 cells transfected with miRNA inhibitors demonstrating an attenuated growth pattern compared to Scramble control cells where CHIKV titers peaked at 48 h. p. i. BHK-21 cells: Cells transfected with MIR-12 and MIR-125 did not exhibit any significant differences in CHIKV titers at any timepoint when compared with Scramble control cells. [score:1]
aegypti saliva were aae-mir-281 (56394), aae-mir-2940 (25307), aae-mir-8 (47613), aae-mir-184 (10105) aae-mir-bantam (9969), aae-mir-263a (9084) and aae-mir125 (5863) (Table 1). [score:1]
albopictus saliva was aae-mir-8 with a count of 12874 followed by aae-mir-2940 (2574), aae-mir-bantam (2127) and aae-mir-125 (2132) (Table 3). [score:1]
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Radiation up-regulated miRNA expression levels included let-7g, miR-16, miR-20a, miR-21 and miR-29c, while miR-18a, miR-125a, miR-127, miR-148b, miR-189 and miR-503 were down-regulated. [score:9]
For miR-125a and -127 we found that the downregulation of the miRNA levels caused a significant reduction (P < 0.05) of clonogenic survival (Figs. 5 and 6, left panels). [score:4]
In functional assays with miR-125a, -127 and -148b we observed weaker effects of miR overexpression or inhibition. [score:4]
Figure 5 Clonogenic survival of HDMEC after transfection with miR-125a precursor or inhibitor. [score:3]
According to our own results miR-125a is also differentially expressed in human fibroblasts by hydrogen peroxide (H [2]O [2]), which is like ionizing radiation a stressor for cells [17]. [score:3]
Notably, the radiosensitivity of HDMEC was significantly influenced by differential expression of miR-125a, -127, -189, and let-7g. [score:3]
When changing levels of miR-125a we found a decrease of clonogenic survival upon inhibition. [score:3]
Accordingly, we found that inhibition of miR-125a had the respective negative effects, comparable to non-RT conditions. [score:3]
The overexpression of miR-125a or miR-127 showed no marked effects on clonogenicity per se. [score:3]
However, the altered expression significantly influenced the response to radiation: Pre-miR-125a enhanced the number of clones compared to irradiated mock control cells, while anti-miR-125a reduced clonogenic survival (P < 0.05) (Fig. 5, right panel). [score:2]
While in particular miR-189 and miR-125a have a protective effect on endothelial cells, miR-127 and let-7g enhance their sensitivity to irradiation. [score:1]
Out of the microRNA list from the microarrays we selected six miRNAs (let-7g, miR-125a, miR-127, miR-148b, miR-189, and miR-20a) for further functional analysis. [score:1]
Similar to miR-189, miR-125a had a positive effect on endothelial clonogenic survival after irradiation. [score:1]
While miR-125a and miR-189 had a radioprotective effect, miR-127 and let-7g enhanced radiosensitivity in human endothelial cells. [score:1]
Six microRNAs (miRs) were chosen for subsequent functional analyses (let-7g, miR-125a, miR-127, miR-148b, miR-189, and miR-20a). [score:1]
We found that especially miR-189, let-7g, and miR-20a seem to play a role in endothelial cell clonogenic survival and/or proliferation, and to a weaker extend also miR-125a, -127, and -148b. [score:1]
The following pre- and anti-miRs were used: hsa-let-7g, hsa-miR-125a, hsa-miR-127, hsa-miR-148b, hsa-miR-189, hsa-miR-20a, pre-miR negative control #1, and anti-miR negative control #1 (all purchased from Ambion). [score:1]
s Out of the microRNA list from the microarrays we selected six miRNAs (let-7g, miR-125a, miR-127, miR-148b, miR-189, and miR-20a) for further functional analysis. [score:1]
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Other miRNAs from this paper: hsa-mir-125b-1, hsa-mir-140, hsa-mir-125b-2, hsa-mir-4319
In this study, miR-125 suppressed ADAMTS-4 mRNA expression by 72% and protein production by 62% following IL-1β stimulation. [score:5]
Expression of ADAMTS-4, ADAMTS-5, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA, mature miR-125a, miR-125b, miR-4319 or U6 small nuclear RNA (RNU6B) was determined using the TaqMan Gene Expression Assay (Applied Biosystems). [score:4]
In this study, we use bioinformatics to predict putative target sequences for miR-125a, miR-125b and miR-4319 in human ADAMTS-4 mRNA. [score:3]
Our results show that miR-125b but not miR-125a is strongly expressed in normal human chondrocytes and cartilage tissues. [score:3]
In normal chondrocytes, miR-125b was strongly expressed while miR-125a and -4319 were barely detectable (Figure 1B). [score:3]
We also predicted target sequence of miR-125a and miR-4319 in 3'-UTR ADAMTS-4 mRNA. [score:3]
TargetScan 6.2 identified a sequence conserved in the 3'-UTR of ADAMTS-4 mRNA that was complementary to the miR-125b (Figure 1A), miR-125a and miR-4319 seed sequences (data not shown). [score:3]
We determined the expression of miR-125b, miR-125a and miR-4319 using quantitative real-time PCR in normal and OA chondrocytes and cartilage tissues. [score:3]
In the luciferase reporter assay, mutation of the putative miR-125b binding site in the ADAMTS-4 3'UTR abrogated the suppressive effect of miR125. [score:3]
Both miR-125a and miR-125b were previously reported to be highly expressed in mouse spinal cord and liver, but only miR-125b was detected in other tissues [23]. [score:3]
The expression of miR-125b was 49-fold higher than miR-125a and approximately two million-fold higher than miR-4319 (Figure 1B). [score:3]
We demonstrate that expression of miR-125b, but not miR-125a and miR-4319, is significantly decreased in human OA chondrocytes compared to normal chondrocytes. [score:2]
However, our results indicate that miR-125a and miR-4319 expression in chondrocytes is very low compared to miR-125b and there are no significant changes in OA chondrocytes (data not shown). [score:2]
Thus, miR-125b, but not miR-125a and miR-4319, may play a role in OA development. [score:2]
Expression of miR-125b, but not miR-125a and -4319, was found to be 54% lower in OA chondrocytes compared to normal chondrocytes (Figure 1C and data not shown). [score:2]
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The gene expression of the processing machinery components (Drosha, DGCR8 and Dicer) and the production of the selected miRNAs (miR-223, miR-92a, miR-486, miR-125a and miR-146a) are presented in Fig 4. The gene expression of Drosha, DGCR8 and Dicer was upregulated in cells incubated with either sera with added glucose compared to the NG sera (an average of 2 fold, p<0.05, Fig 4A). [score:7]
Pro-inflammatory M1 macrophages exhibit an increased expression of miR-125a [37], which could also be a protective feedback mechanism, because the inhibition of the endogenous miR-125a levels in THP-1 macrophages increases the secretion of inflammatory cytokines and the expression of macrophage scavenger receptors resulting in increased lipid uptake [38]. [score:7]
Exposure of human macrophages to ACS sera compared to SA sera determines an increase of the production of miR-223, miR-92a, miR-486, miR-125a and miR-146a by the upregulation of Drosha, DGCR8 and Dicer expression, this effect being augmented by the increase of sera’s glucose concentration. [score:5]
Moreover, only miR-125a and miR-146a levels expressed a significant increase in human macrophages exposed to SA+Gluc sera compared to NG, SA sera, in good correlation with the increase of the gene expression of Drosha, DGCR8 and Dicer. [score:4]
The gene expression of the processing machinery proteins (Drosha, DGCR8 and Dicer) and the selected miRNAs (miR-223, miR-92a, miR-486, miR-125a and miR-146a) levels are presented in Fig 3. 10.1371/journal. [score:3]
The gene expression of the processing machinery proteins (Drosha, DGCR8 and Dicer) and the selected miRNAs (miR-223, miR-92a, miR-486, miR-125a and miR-146a) levels are presented in Fig 3. 10.1371/journal. [score:3]
Levels of miR-223 (A), miR-92a (B), miR-486 (C), miR-122 (D), miR-125a (E), miR-146a (F) in sera from Control subjects and coronary artery disease (CAD) patients with stable angina (SA) or acute coronary syndrome (ACS), with/without hyperglycemia. [score:3]
We also observed that miR-125a expressed the highest increase in macrophages incubated with ACS+Gluc sera compared to NG, ACS sera (2 fold, p<0.05). [score:2]
We report that the exposure of human macrophages to ACS sera induces the increase of the intracellular miR-223, miR-92a, miR-486, miR-125a and miR-146a levels in human macrophages, the highest levels being observed for miR-486 and miR-92a. [score:1]
We then added miR-125a and miR-146a, based on preliminary data about hyperglycemia-related effects [25]. [score:1]
In this study, we evaluated the levels of a panel of six miRNAs (miR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a) in sera and HDL from stable angina (SA) and ACS patients, and the functional effects of ACS and SA patients’ sera, with or without hyperglycemia, on cultured human macrophages, namely on the gene expression of the processing machinery proteins (Dicer, Drosha, DGCR8) and analyzed miRNAs production. [score:1]
The new data about the effect of hyperglycemia on miRNAs obtained in the present study are: (i) in hyperglycemic ACS sera, miR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels are increased compared to the normoglycemic ACS sera; (ii) in HDL from hyperglycemic ACS compared to normoglycemic sera, miR-223, miR-92a, miR-486 are increased and statistically different between ACS and SA patients; (iii) ACS sera induce an increase of Drosha, DGCR8 and Dicer expression and of miR-223, miR-92a, miR-486, miR-125a and miR-146a production in human macrophages; (iv) the hyperglycemic sera augments the effects observed in human macrophages exposed to normoglycemic sera, mainly in the case of ACS sera. [score:1]
The serum and Lp levels of Homo sapiens (hsa)-miR-223-3p (ID002295), hsa-miR-92a-3p (ID000431), hsa-miR-486-5p (ID001278), hsa-miR-122-5p (ID002245), hsa-miR-125a-5p (ID002198), hsa-miR-146a-5p (ID000468) and cel-miR-39-5p (ID000200) were determined by employing the TaqMan technology. [score:1]
The addition of glucose to normoglycemic sera (to mimic the existing concentration in hyperglycemic ones) induces both an increase of the miRNAs (miR-125a, miR-486, miR-92a, miR-146a, and miR-223) levels and of their processing machinery proteins (Drosha, DGCR8 and Dicer). [score:1]
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25
[+] score: 40
Expression of 12 miRNA upregulated in TGF-β -treated cells both resembled and differed in iron -treated cells: 6 miRNA were similarly upregulated, hsa-miR-7a, -7d, -7e, -23a, -30c, and -574-5p; 2 miRNA were downregulated, hsa-miR-125a-5p and -21; and expression of 4 miRNA was unchanged, hsa-miR-146a, -23b, -483-5p, and -99b. [score:14]
The level of miRNA expression change was also lower, since Log2 fold decreases ranged from −1.25 (hsa-miR-221) to −4.64 (hsa-miR-605) and Log2 fold increases ranged from 1.14 (hsa-miR-23b) to 2.87 (hsa-miR-125a-5p). [score:3]
Expression of miR-125a-5p and -151-5p antagomirs did not affect iron -induced HBV replication. [score:3]
Treatment of cells with antagonists of miR-125a-5p did not reverse TGF-β -induced suppression of HBV replication (Fig. 4B ). [score:3]
For these studies, 2.2.15 cells were transfected with miRNA mimics or miRNA antagonists followed by administration to transduced cells of either 20 ng/ml TGF-β or 100 µM iron for 48 h. (A) Changes in iron -treated cells are shown after expression of miR-125a-5p or -151-5p mimics. [score:3]
0039276.g004 Figure 4 For these studies, 2.2.15 cells were transfected with miRNA mimics or miRNA antagonists followed by administration to transduced cells of either 20 ng/ml TGF-β or 100 µM iron for 48 h. (A) Changes in iron -treated cells are shown after expression of miR-125a-5p or -151-5p mimics. [score:3]
Mimics of miR-125a-5p and -151-5p did not affect TGF-β -induced inhibition of HBV replication. [score:3]
The counter-regulation in TGF-β- and iron -treated cells of hsa-miR-125a-5p and -21 was of interest, since these, and other miRNA, may have contributed in HBV replication. [score:2]
06 hsa-miR-595 5.29 hsa-miR-92b −9.97 hsa-miR-601 5.88 hsa-miR-765 4.47 hsa-miR-98 5.05 hsa-miR-99a 6.41 TGF-β -treated hsa-miR-20b −1.29 hsa-let-7a 1.38 hsa-miR-221 −1.25 hsa-let-7d 1.43 hsa-miR-605 −4.64 hsa-let-7e 2 hsa-miR-638 −1.40 hsa-miR-125a-5p 2.87 hsa-miR-663 −2.06 hsa-miR-146a 2.72 hsa-miR-720 −2.40 hsa-miR-21 1.14 hsa-miR-23a 1.20 hsa-miR-23b 1.14 hsa-miR-30c 1.89 hsa-miR-483-5p 1.38 hsa-miR-574-5p 2.23 hsa-miR-99b 1.63 10.1371/journal. [score:1]
In response to miR-125a-5p and -151-5p mimics, iron -induced HBV replication declined in dose -dependent fashion by up to 23% and 45%, respectively, p<0.05 (Fig. 4A ). [score:1]
Several anti-HBV miRNA were previously reported, e. g., hsa-miR-125-5p, -125-b, -151-5p, -199a-3p, -122, etc. [score:1]
As hsa-miR-125a-5p and -151-5p mimics prevented iron -induced increases in HBV replication, while their antagonists prevented TGF-β -induced decreases in HBV replication, this established miRNA were the principal intracellular effectors of TGF-β/BMP signaling. [score:1]
06 hsa-miR-595 5.29 hsa-miR-92b −9.97 hsa-miR-601 5.88 hsa-miR-765 4.47 hsa-miR-98 5.05 hsa-miR-99a 6.41 TGF-β -treated hsa-miR-20b −1.29 hsa-let-7a 1.38 hsa-miR-221 −1.25 hsa-let-7d 1.43 hsa-miR-605 −4.64 hsa-let-7e 2 hsa-miR-638 −1.40 hsa-miR-125a-5p 2.87 hsa-miR-663 −2.06 hsa-miR-146a 2.72 hsa-miR-720 −2.40 hsa-miR-21 1.14 hsa-miR-23a 1.20 hsa-miR-23b 1.14 hsa-miR-30c 1.89 hsa-miR-483-5p 1.38 hsa-miR-574-5p 2.23 hsa-miR-99b 1.63 10.1371/journal. [score:1]
We selected miR-125a-5p and -151-5p for analyzing their effects on HBV replication. [score:1]
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[+] score: 39
Target mRNAs (TargetScan, negatively correlated) Cell Type specificity HSA-MIR-223 82 Monocytes; Eosinophils; Neutrophils HSA-MIR-143 60 Neutrophils HSA-MIR-150 27 B cells; T cells; NK cells HSA-MIR-500 25 Monocytes; pDCs HSA-MIR-652 11 Monocytes; Eosinophils; Neutrophils HSA-MIR-125A 9 T cells; Neutrophils To further support our observations, we searched for studies in which cell-type specific miRNA expression levels were altered by either over -expression or knock-out, and asked if the genes we had identified as miRNA targets were correspondingly up- or down-regulated in response. [score:15]
Target mRNAs (TargetScan, negatively correlated) Cell Type specificity HSA-MIR-223 82 Monocytes; Eosinophils; Neutrophils HSA-MIR-143 60 Neutrophils HSA-MIR-150 27 B cells; T cells; NK cells HSA-MIR-500 25 Monocytes; pDCs HSA-MIR-652 11 Monocytes; Eosinophils; Neutrophils HSA-MIR-125A 9 T cells; Neutrophils 696 genes were specifically up or down-regulated in one, two or three different cell-types, with the majority of genes (542) uniquely up or down-regulated in a single cell-type. [score:11]
miR-125a-5p, which we found in our study specifically expressed in T cells, was also found to be expressed by CD4 and CD8 cells, in the study of Rossi et al. In concordance with their results we also found expression of miR-150 in all B, T and NK cells subsets. [score:7]
Similarly, miR-125 was expressed in neutrophils and T cells, 14.1 fold higher than in eosinophils. [score:3]
miR-362 and miR-125 were specific to two cells types. [score:1]
Six of these miRNAs (miR-223, miR-143, miR-150, miR-500, miR-652 and miR-125) were cell-type specific based on our previous analysis. [score:1]
A) miR-143 and miR-31 were specific to neutrophils and T cells respectively, while B) miR-362 and miR-125 were specific to monocytes, pDCs and T cells, neutrophils. [score:1]
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[+] score: 38
Although Lin28 and Bak1 have been proposed as the critical targets of miR-125a/b for regulating these stem cell compartments [8], [9], the hundreds of predicted targets for miR-125a/b suggest a more complex interplay between miR-125a/b and its targets in regulating proliferation and differentiation. [score:9]
miR-125a-AS was co -transfected with miR-125b-AS to achieve a complete silencing of the miR-125a/b family, because miR-125a, which shares the same seed sequence and the same predicted targets as miR-125b, is also highly expressed in human and mouse fibroblasts (Figure S1C, S1D). [score:5]
Overexpression of miR-125a/b causes an expansion of mammalian hematopoietic stem cells (HSCs) and aberrant differentiation, leading to myeloid leukemia [9], [10] and also lymphoid leukemia if miR-125b is overexpressed in fetal liver HSC-enriched cells [12]. [score:5]
Genes that were either significantly repressed by miR-125b or significantly derepressed by miR-125a/b-AS with fold-changes within the range of microRNA regulation (P<0.05, fold change > 1.3), were selected as candidate miR-125b targets (Figure 2B–2D). [score:4]
However, the molecular underpinnings of miR-125a/b's regulation of tissue stem cell homeostasis had remained unclear largely due to the complex nature of microRNA regulation of gene networks. [score:3]
In mice, out of 22 predicted targets in the p53 network, 11 genes were derepressed by miR-125a/b-AS in 3T3 cells and 12 genes were repressed by miR-125b in N2A cells (Figure 2C). [score:3]
Much like lin-4′s role of regulating the homeostasis of reiterative or self-renewing stem cells in C. elegans [6], recent studies have shown that miR-125a/b regulates mammalian neural stem cell commitment, as well as the mammalian hematopoietic stem cell (HSC) pool size [7]– [10]. [score:3]
Our GOF/LOF screen revealed that in humans, out of 29 predicted targets in the p53 network, 13 genes were derepressed by miR-125a/b-AS in hLF cells and 20 genes were repressed by miR-125b in SH-SY5Y cells (Figure 2B). [score:3]
1002242.g002 Figure 2(A) Loss-of-function (LOF) screens were performed in human primary lung fibroblasts (hLF) or mouse 3T3 fibroblasts by transfecting an antisense RNA against both miR-125a and miR-125b (miR-125a/b-AS), or by microinjecting morpholinos (MO) against pre- mir-125b hairpin precursors (all 3 isoforms) into zebrafish embryos. [score:1]
Several miRNAs are conserved in metazoan evolution, one prominent example being lin-4 whose vertebrate homologues comprise the miR-125a/b family [5]. [score:1]
In all panels, the levels of miR-125a and miR-125b were quantified by real-time PCR, and presented as log [2] (fold change) ± s. e. m. (n≥3) relative to the levelsof RNU6B loading control. [score:1]
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[+] score: 38
In the current study, we provide potential miRNAs that could be used to restrict transgene expression to a particular blood cell type (Tables S6 and S7), and demonstrated reporter gene expression could be regulated by endogenous levels of miR-125a-5p; high levels of miR-125a-5p suppressed expression in a megakaryocytic cell line (Meg-01), whereas low levels of miR-125a-5p permitted expression in the lymphocytic-like cell lines (Raji and Jurkat). [score:12]
To assess whether miR-125a-5p directly alters reporter gene repression, we co -transfected Luc-4x125a with an inhibitor of miR-125a-5p and observed enhanced expression in Meg-01 cells, whereas over -expression of miR-125a-5p repressed reporter gene expression in Jurkat cells (Figure 5E). [score:10]
To test the hypothesis that endogenous miRNA levels could be exploited to modify transgene expression, we selected miR-125a-5p, which was expressed at very low levels in the lymphocytic cell lines, Jurkat and Raji, and high levels in Meg-01 and K562 cells (Figure 5A). [score:5]
Thus, we cannot extrapolate that miR-125a-5p would be a useful target for restricting transgene expression in primary cells. [score:5]
One, two or four miRNA binding site sequences for miR-125a-5p or a scrambled control sequence were engineered into a luciferase 3′UTR using pMIR-REPORT vector (Applied Biosystem, Carlsbad, CA, USA) followed by sub-cloning into the pCDH-MSCV-MCS-EF1-GFP vector (System Biosciences). [score:1]
Luciferase repression was enhanced with more miR-125a-5p binding sites. [score:1]
Constructs were engineered to contain 1, 2 or 4 miR-125a-5p binding sites or scrambled sequence controls. [score:1]
Jurkat cells were co -transfected with Luc-4x125 construct and control pre-miRNA or pre- miR-125a-5p. [score:1]
We generated a construct containing a luciferase reporter with a 3′UTR containing 1, 2 or 4 tandem miR-125a-5p binding sites or scrambled control (Figure 5B). [score:1]
0102259.g005 Figure 5(A) Illustration that miR-125a-5p was selectively reduced in the lymphocytic cell lines, Jurkat and Raji. [score:1]
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[+] score: 37
In the host tissue of the liver metastases, we identified several miRNAs with significant correlations between expression and survival: downregulation of miR-125 (p = 0.05), miR-127 (p = 0.001), miR-145 (p = 0.005), miR-192 (p = 0.015), miR-194 (0.003), miR-199-5 (p = 0.008), miR-215 (p < 0.001), and miR-429 (p = 0.03) was associated significantly with poor survival (Table 4). [score:6]
Downregulation of miR-125 (p = 0.05), miR-127 (p = 0.001), miR-145 (p = 0.005), miR-192 (p = 0.015), miR-194 (p = 0.003), miR-199-5 (p = 0.008), miR-215 (p < 0.001), and miR-429 (p = 0.03) in the normal liver tissue was significantly associated with poor survival, suggesting oncosuppressive effects of these miRNAs. [score:6]
In the lung metastases, miR-125 showed a 40-fold upregulation in the stroma compartment compared to the tumor compartment (p < 0.0001) and a 7-fold upregulation compared to the normal lung tissue (p = 0.008). [score:5]
miR-125 showed a 200-fold upregulation in the stroma compartment of the liver metastases compared to the tumor (p < 0.0001) but no significant upregulation compared to the normal liver tissue. [score:5]
Both miR-125 and miR-199a were shown to inhibit angiogenesis through decreased expression of HIF‑1a (Hypoxia-inducible factor 1-alpha) and VEGF (Vascular Endothelial Growth Factor) in ovarian cancer [24]. [score:5]
Our findings show consistent results with a downregulation of miR-125 and miR-145 in the cancer compartment. [score:4]
miR-125 and miR-199-5 showed a 2-fold; miR-19 and miR-127 showed a 4-fold; miR-215 showed a 100-fold; miR-194 showed a 150-fold; and miR-192 showed a 300-fold upregulation in the normal liver tissue compared to the normal lung tissue. [score:3]
miR-194 showed a 1.5-fold; miR-125, miR-127, and miR-192 showed a 2.5-fold; miR-19 and miR-215 a 3-fold; miR-145, miR-199-3, and miR-429 a 5-fold; miR-21 a 7-fold; and miR-199-5 a 12.5-fold downregulation in the liver metastases compared to the lung metastases. [score:3]
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[+] score: 37
For instance, miR-99b was found to target the 3′ UTRs of IGF1R, miR-125a targeted ETV6, TNFAIP3 and CX3CR1, and let7e targeted TNFAIP3 and ITGA4. [score:7]
To perform the miRNA inhibitor experiments, we used unlabeled miRCURY LNA™ microRNA Power inhibitors to inhibit miR-99b (reference 4101513), miR-let-7e (reference 4103550), miR-125a (reference 4103094), miR-132 (reference 4103093), miR-212 (reference 4104787) or a control (Negative Control A, reference 199006) Exiqon, Vedbaek, Denmark. [score:7]
These assays confirmed that miR-99b targets IGF1R, miR-125a targets TNFAIP3, and let-7e targets ITGA4 and THBS1. [score:6]
In the case of the miR-99b/let-7e/125a cluster, inhibition of miR-99, miR-125a and let-7e resulted in the specific upregulation of IGF1R, TNFAIP3 and IGF1R, and of ITGA4 and THBS1, respectively. [score:6]
The raw expression data are listed in full in Additional file 1. The array expression data were validated in the samples used (validation set), and in a larger cohort of samples obtained from independent donors (replication set) using Exiqon microRNA LNA™ PCR primer sets (hsa-miR-99b-5p, reference 204367; hsa-miR-125a-5p, reference 204339; hsa-miR-132-3p, reference 204129; hsa-miR-212-3p, reference 204170; hsa-miR-103a-3p, reference 204063). [score:4]
Our results show that IGF1R is targeted by miR99b and miR125a also suggesting a coordinated shutdown of signal transduction that block NF-κB pathways. [score:3]
For instance, inhibition of miR-99b and miR-125a also affected PTGS2, which was not validated in luciferase assays but also contains putative recognition sites at its 3′ UTR for miR-99b and miR-125. [score:2]
An opposite effect was observed for the MO-specific gene CX3CR1 with miR-99b and miR-125a (Figure  2B). [score:1]
For example, miR-99b and miR-125a levels are increased by 300-fold and 100-fold respectively, whereas miR-let-7e induction is only increased by 10- to 12-fold. [score:1]
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[+] score: 32
Of the 186 miRNAs the expression of which was altered, nine were up-regulated at both time points (miR-125a-3p, miR-297c, miR-421, miR-452, miR-483, miR-574-3p, miR-574-5p, miR-669a, miR-720) and 11 were down-regulated at both time points (let-7g, miR-107, miR-10a, miR-15a, miR-15b, miR-199b*, miR-26a, miR-29c, miR-324-5p, miR-331-3p, miR-342-3p). [score:9]
In TM4 cells exposed to NP, Ppara was down-regulated at both 3 and 24 h. We thus surmised that miRNAs regulated by Ppara may include miR-378, miR-125a-3p, and miRNA-148a at 3 h, and miR-20a, miR-203, and miR-101a at 24 h. Figure 3 Network analysis of miRNAs the expression of which in TM4 cells was altered by NP (A) 3 h. (B) 24 h. Network analysis was performed using an algorithm supported by IPA. [score:7]
In TM4 cells exposed to NP, Ppara was down-regulated at both 3 and 24 h. We thus surmised that miRNAs regulated by Ppara may include miR-378, miR-125a-3p, and miRNA-148a at 3 h, and miR-20a, miR-203, and miR-101a at 24 h. Figure 3 Network analysis of miRNAs the expression of which in TM4 cells was altered by NP (A) 3 h. (B) 24 h. Network analysis was performed using an algorithm supported by IPA. [score:7]
Network analysis of deregulated miRNAs suggested that Ppara may regulate the expression of certain miRNAs, including miR-378, miR-125a-3p miR-20a, miR-203, and miR-101a, after exposure to NP. [score:5]
miR-125a-3p and miR-107 are also involved in cell cycle and it is known that their expression is regulated by PPARA [23]. [score:4]
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[+] score: 31
Xu et al. showed that ectopic expression of miR-125a-5p significantly inhibited growth of gastric cancer cells by directly targeting E2F3 [62]. [score:8]
In gastric cancer, suppression of miR-125a-5p was observed to promote tumor metastasis, while upregulation of miR-125a-5p substantially reduced the capacities of migration and invasion [62]. [score:6]
A recent study has shown that downregulation of miR-125a-5p was involved in gastric carcinogenesis by targeting E2F3 [62]. [score:6]
It was also reported that miR-125a-5p could function as a negative regulator of C2C12 myoblast proliferation via regulation of E2F3 [61]. [score:3]
In addition, miR-125a-5p and E2F3 displayed reversely associated expression pattern in the proliferative phase of C2C12 myoblasts [61]. [score:3]
Augment of miR-125a-5p affected DNA replication and promoted G1 arrest by regulating E2F3 [61]. [score:2]
It was also confirmed that miR-125 and miR-106a were upstream regulators of E2F3 and RB1, respectively, via the mechanisms involved cisplatin -induced K562 cell apoptosis [88]. [score:2]
The three members of miR-125 family (miR-125a, miR-125b-1 and miR-125b-2) have been found to function as either promoter or repressor in different cancers [61]. [score:1]
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A comprehensive list of potential miRNA targets for AML therapy is summarized in Table 2. Table 2 miRNA target genes or pathways References miR-141 PI3K/Akt/mTOR[113] miR-125a ErbB pathway[10] miR-125b Mcl-1[11, 12] miR-22-3p, let-7e-5p PLK1[114] miR-34a PD-L1[80] miR-638 CDK2[34] miR-181a, b and c PRKCD, CTDSPL and CAMKK1[6, 36, 96, 97] miR-191-5p, miR-142-3p PPP2R2A[19, 115] miR-181b MDR[36] miR-21, miR-196b HOX[98] miR-29a/b/c Dnmts[19, 22] Both single miRNAs and panel of miRNAs have potential prognostic value complementing information gained from cytogenetics, gene mutations, and altered gene expression. [score:8]
The standard chemotherapy agent for AML, decitabine, also a de-methylating agent could significantly restore the expression of miR-125a through suppressing the global methylation in AML cell lines. [score:5]
These findings indicate the potential of miR-125a as a new therapeutic target for miR-125a-low AML [10]. [score:3]
In AML NB4 cells ectopically expressing miR-125a ErbB pathway was significantly activated. [score:3]
miR-125a expression in cytogenetically normal AML (CN-AML) was most decreased in favorable and intermediate prognostic populations and associated with decreased survival [10]. [score:3]
Furthermore, analysis of the upstream region of miR-125a and bisulfite sequencing revealed that miR-125a is suppressed by methylation in AML. [score:3]
While studies of miR-125a suggested it has a tumor suppressor role in AML, miR-125b is considered as an oncomiRNA. [score:2]
The miR-125 family exists as three homologues (miR-125a, b, and c) all on different chromosomes. [score:1]
In AML, ErbB receptors ErbB-1 and ErbB-3 were the main mediators of miR-125a, and the phosphorylation of the downstream effectors AKT and MAPK played key roles in driving proliferation and survival of the AML blasts. [score:1]
For example, HSC self-renewal can be governed by miR-125a/b, miR-29a, and miR-126 [40, 43- 45]. [score:1]
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miR-125a-5p and miR-125b-5p (but not miR-134-3p or miR-495-3p) altered CYP11B2 expression in vitro through direct targeting of its transcript 3′UTR. [score:6]
The miR-125 family has been implicated in the regulation of several cell types and has many confirmed targets, including vascular cell cycle-related genes of importance in hypertension [34, 35]. [score:4]
In order to identify individual miRNAs contributing to the net miRNA effect, as observed under Dicer1 knockdown, four miRNAs (miR-125a-5p, miR-125b-5p, miR-134-3p, and miR-495-3p) expressed in human adrenal tissue and with putative binding sites in the 3′UTR of CYP11B2 were selected for further study. [score:4]
The miR-125 Family Regulates CYP11B2 mRNA Expression. [score:4]
miR-125a-5p expression was lower in APA. [score:3]
This is borne out by the fact that qRT-PCR analysis of specific miRNA levels in the Dicer1 knockdown cells showed no significant reduction on the levels of the miRNAs miR-125a-5p, miR-125b-5p, miR-134-3p, miR-320a-3p, and miR-495-3p relative to controls (data not shown). [score:2]
Of the five miRNAs investigated in the current study, two (miR-125a-5p and miR-495-3p) were expressed at significantly lower levels in APA tissue relative to nontumorous tissue; one (miR-320a-3p) was significantly increased in APA tissue and two (miR-125b-5p and miR-134-3p) did not differ significantly between the tissue types (Figure 6). [score:1]
However, the presence of active binding sites predicted for miR-125a-5p and miR-125b-5p was confirmed by changes in luciferase activity. [score:1]
Increasing the levels of miR-125a-5p in Pre-miR -transfected cells reduced luciferase activity to 63.78 ± 8.70% (p = 0.011) while reduction of miR-125a-5p levels in Anti-miR -transfected cells significantly increased luciferase activity to 173.72 ± 22.54% (p = 0.040). [score:1]
However, miR-125a is located on human chromosome 19 in a cluster with miR-99b and let-7c, while miR-125b can originate from either human chromosome 11 (miR-125b-1) or human chromosome 21 (miR-125b-2). [score:1]
Here, miR-125a-5p Pre-miR decreased CYP11B2 mRNA abundance (0.69 ± 0.002-fold; p < 0.0001), while its Anti-miR significantly increased it (1.62 ± 0.014-fold p = 0.011; Figure 4(e)). [score:1]
Pre-miR™ or Anti-miR™ molecules (miR-125a-5p: product code 12561; miR-125b-5p miR-134-3p 10341; miR-495-3p: 11526; and miR-320a-3p: 11621, Applied Biosystems) were transfected to a final concentration of 50 nM and prevalidated siRNA molecules (Dicer 1A: product code s23755; Dicer 1B: s23756, Applied Biosystems) to a final concentration of 30 nM. [score:1]
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[+] score: 29
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-101-1, hsa-mir-106a, hsa-mir-107, hsa-mir-16-2, hsa-mir-192, hsa-mir-196a-1, hsa-mir-199a-1, hsa-mir-129-1, hsa-mir-148a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-196a-2, hsa-mir-199a-2, hsa-mir-203a, hsa-mir-210, hsa-mir-212, hsa-mir-214, hsa-mir-215, hsa-mir-217, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-27b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-129-2, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-195, hsa-mir-206, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-200a, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-130b, hsa-mir-376c, hsa-mir-375, hsa-mir-378a, hsa-mir-148b, hsa-mir-338, hsa-mir-335, hsa-mir-423, hsa-mir-20b, hsa-mir-429, hsa-mir-449a, hsa-mir-433, hsa-mir-451a, hsa-mir-193b, hsa-mir-520d, hsa-mir-503, hsa-mir-92b, hsa-mir-610, hsa-mir-630, hsa-mir-650, hsa-mir-449b, hsa-mir-421, hsa-mir-449c, hsa-mir-378d-2, hsa-mir-744, hsa-mir-1207, hsa-mir-1266, hsa-mir-378b, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-4512, hsa-mir-378i, hsa-mir-203b, hsa-mir-451b, hsa-mir-378j
In addition, the tumor suppressor miR-125a, which targets ERBB2 (erb-b2 receptor tyrosine kinase 2), and miR-129, which targets CDK6 (cyclin -dependent kinase 6), are also involved in anti-proliferative and pro-apoptotic functions [24, 126, 127, 131]. [score:7]
Xu Y. Huang Z. Liu Y. Reduced miR-125a-5p expression is associated with gastric carcinogenesis through the targeting of E2F3 Mol. [score:5]
Moreover, GC patients with over -expression of miR-107 [28, 29, 30], miR-143 [40], miR-145 [41, 42], miR-181b/c [17, 47, 48, 55, 56], miR-196a/b [59], miR-20b [23, 66], miR-23a/b [77, 78, 79], miR-34 [17, 47, 48, 55, 56] and miR-630 [100] and decreased expression of miR-1 [111], miR-1207-5p [121], miR-125a-3p/-5p [24, 125, 126, 127], miR-185 [140], miR-193b [60], miR-20a [111], miR-206 [150, 151], miR-215 [142], miR-217 [153], miR-27a [111], miR-29c [169], miR-34a [172, 173], miR-423-5p [111], and miR-520d-3p [99] indicate advanced tumor stage or TNM stage. [score:5]
Hashiguchi Y. Nishida N. Mimori K. Sudo T. Tanaka F. Shibata K. Ishii H. Mochizuki H. Hase K. Doki Y. Down-regulation of miR-125a-3p in human gastric cancer and its clinicopathological significance Int. [score:4]
In addition, oncomiR-20b, miR-150 [23], miR-214 [24, 74], miR-375 [39, 74, 86, 87, 88], tumor suppressor Let-7g [24, 109, 110], miR-125-5p [126], miR-146a [24, 134], miR-218 [154], miR-433 [24, 86, 109, 110, 174], and miR-451 [24, 94, 230] are associated with a poor survival prediction in GC. [score:3]
Conversely, the tumor suppressors miR-125a and miR146a are significantly correlated with lymph node metastasis, indicating that they could be prognostic factors of overall survival [126, 134]. [score:3]
Nishida N. Mimori K. Fabbri M. Yokobori T. Sudo T. Tanaka F. Shibata K. Ishii H. Doki Y. Mori M. MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab Clin. [score:2]
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[+] score: 29
Real time analysis showed up-regulation of miR-125a-5p in 45,X and 47,XXX cells and as expected its target gene HOXC4 has low expression (Fig. 4A,). [score:8]
Transfection of miR-125a-5p mimic affected the expression of validated target gene HOXC4 where in X monosomy it showed increased transcription while in 46,XX cells it was down regulated but there was no effect in 47,XXX cells. [score:6]
Out of these 5 genes HOXC4 is a validated target for miR-125a-5p while BNC1, SLC2A14, LMCD1 are validated targets of miR- 335-5p. [score:5]
Transfection experiments demonstrate that in X aneuploidy miR-125a-5p and miR-335-3p can regulate the expression of a few genes. [score:4]
Further analysis using DIANA LncBase V2 experimental module 51 led to identification of 4 (miR-10b-5p, miR-125a-5p, miR-4325 and miR-615-5p) differentially expressed miRNAs which can interact with lncRNA Xist. [score:3]
Real time PCR analysis showed both miRNA mimics (hsa-miR-125a-5p and 335-5p) have successfully been transfected in all X aneuploidy cells since increased expression (Unpaired t-test P < 0.05) of both miRNAs could be seen as compared to control (Supplementary Figure S3). [score:2]
These cells were transfected with Qiagen micro RNA mimics for hsa-hsa-miR-125a-5p (MSY0000443), hsa-miR-335-5p (MSY0000765) and All Stars negative control siRNA (1027281) using HiPerFect transfection reagent (Qiagen Cat. [score:1]
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[+] score: 28
Overexpression of miR-125a-5p inhibited LPS -induced M1 marker expression while enhancing the expression of IL-4 -induced M2 markers. [score:9]
Through targeting of FIH and IRF4, miR-125a has been reported to promote M1 and suppress M2 phenotype (113). [score:5]
Czimmerer et al. profiled miRNA expression in IL-4 -mediated activation and identified miR-342-3p, miR-99b, and miR-125a-5p as regulators of MΦ survival (83). [score:4]
Their initial finding was that miR-125a-5p is expressed at a higher level in M-BMM than GM-BMM. [score:3]
Furthermore, the opposite was true when miR-125a-5p expression was silenced. [score:3]
They subsequently showed that miR-125a-5p expression was increased by TLR4/2 ligation and provided evidence that miR-125a-5p is part of the negative feedback loop that exists to reign back the pro-inflammatory potential of the innately activated MΦ. [score:3]
miR-125a is also known to modulate TAM differentiation and function. [score:1]
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[+] score: 27
Auxiliary pairing regulates miRNA–target specificity in vivoAs a striking indication that auxiliary pairing regulates miRNA–target specificity, duplex structure analysis revealed distinct binding patterns for members of miRNA seed families (for example, let-7, miR-30, miR-181 and miR-125) (Fig. 4d). [score:7]
identified functional, non-canonical regulation globally for miR-128 and miR-124 (Fig. 2), and for individual miR-9, miR-181, miR-30 and miR-125 targets (Fig. 4f and Fig. 8b–m). [score:4]
As a striking indication that auxiliary pairing regulates miRNA–target specificity, duplex structure analysis revealed distinct binding patterns for members of miRNA seed families (for example, let-7, miR-30, miR-181 and miR-125) (Fig. 4d). [score:4]
Constructs expressing miR-30a from the miR-30c locus and miR-125b from the miR-125a locus were also made, in an effort to control for processing efficiency. [score:3]
We examined miR-30a, miR-30c and miR-125a targets sites predicted to form more stable pairing with a specific paralogue and which were ligated to only that paralogue in at least two experiments. [score:3]
Analysis of miR-125 and miR-181 families revealed additional intra -family target preferences (Supplementary Fig. 9a–d). [score:3]
Evaluation of miR-125a (blue), miR-125b (red) and negative control miRNA (black) overexpression on (j) a miR-30 site as a negative control for miR-125 paralogs and (k– m) sites with predicted miR-125a preference. [score:1]
Mouse miR-125a construct was purchased from SBI (MMIR-125a-PA-1). [score:1]
Evaluation of miR-30a (red), miR-30c (blue) and negative control miRNA (black) overexpression on (b) a full miR-30 8mer site as a positive control for miR-30 paralogues; (c) a miR-125 site as a negative control for miR-30 paralogues; (d, e) sites with predicted miR-30a preference; and (f– i) sites with predicted miR-30c preference. [score:1]
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[+] score: 27
An example is the proposed conservation of the miRNA–target relationship lin-4:lin-28 (we use the notation miRNA:mRNA for a miRNA–target pair), first discovered in worm (Moss and Tang 2003): we detect target sites in human lin-28 for the lin-4 miRNA homolog miR-125. [score:7]
miR-124a and miR-125, both highly and specifically expressed in brain, preferentially target RNA -binding proteins. [score:5]
PSD95 is a high-ranking target of miR-125, miR-135, miR-320, and miR-327, all of which are either exclusively expressed in brain or enriched in brain tissue (Lagos-Quintana et al. 2002; Krichevsky et al. 2003; Sempere et al. 2004). [score:5]
One of the miRNA (miR-125) target sites overlaps with the G-quartets, raising the possibility that miRNAs directly compete with FMRP to bind the message in this location. [score:4]
The human homolog of lin-41 (sequence provided by F. J. Slack, personal communication) and another closely related gene (encoding Tripartite motif protein 2) are predicted as high-ranking targets of let-7 and miR-125 (the human homolog of lin-4) (see Tables S2 and S3). [score:3]
In summary, the predicted target sites on human lin-28 are miR-125 (1 site), let-7b (2 sites; Moss and Tang 2003), miR-98 (2 sites), and miR-351 (1 site). [score:3]
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[+] score: 25
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-30a, hsa-mir-31, hsa-mir-98, hsa-mir-99a, hsa-mir-101-1, hsa-mir-16-2, hsa-mir-192, hsa-mir-197, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-187, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-211, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-144, hsa-mir-145, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-138-1, hsa-mir-146a, hsa-mir-200c, hsa-mir-155, hsa-mir-128-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-375, hsa-mir-328, hsa-mir-337, hsa-mir-338, hsa-mir-339, hsa-mir-384, hsa-mir-424, hsa-mir-429, hsa-mir-449a, hsa-mir-485, hsa-mir-146b, hsa-mir-494, hsa-mir-497, hsa-mir-498, hsa-mir-520a, hsa-mir-518f, hsa-mir-499a, hsa-mir-509-1, hsa-mir-574, hsa-mir-582, hsa-mir-606, hsa-mir-629, hsa-mir-449b, hsa-mir-449c, hsa-mir-509-2, hsa-mir-874, hsa-mir-744, hsa-mir-208b, hsa-mir-509-3, hsa-mir-1246, hsa-mir-1248, hsa-mir-219b, hsa-mir-203b, hsa-mir-499b
Targets of the most remarkably down-regulated miRNAs (let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR-122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223) regulate proliferation, gene expression, stress response, apoptosis, and angiogenesis. [score:9]
Microarray analysis of nasal mucosa identified several miRNAs with altered expression in acute RSV -positive infants (down-regulated miR-34b, miR-34c, miR-125b, miR-29c, mir125a, miR-429 and miR-27b and up-regulated miR-155, miR-31, miR-203a, miR-16 and let-7d) as compared to healthy infants [86]. [score:8]
They found three polymorphisms in miR-99b/let-7e/hsa-miR-125a gene cluster derived from the same precursor that influence maturation of their primary transcripts and deltaF508- CFTR mutation can induce an upregulation of miR-99b and miR-125a gene expression, indicating that these miRNAs are important in CF pathogenesis. [score:7]
Endale Ahanda M. L. Bienvenu T. Sermet-Gau delus I. Mazzolini L. E delman A. Zoorob R. Davezac N. The hsa-miR-125a/hsa-let-7e/hsa-miR-99b cluster is potentially implicated in cystic fibrosis pathogenesisJ. [score:1]
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[+] score: 25
We observed in our tumor samples a downregulation of miR-125a-5p, miR-125b, miR-126, miR-145 and let-7g genes, which have been shown to be related to hormonal settings and ErbB2 status of the tumor: miR-125a-5p and miR-125b downregulate ErbB2 and ErbB3 expression [31], miR-126 and let-7g are upregulated in ErbB2 -negative tumors, whereas miR-145 is upregulated in ErbB2 -negative tumors and upregulated in estrogen-receptor -positive and progesterone-receptor -positive tumors [13]. [score:18]
On the other hand, miR-145 [10, 20], miR-10b [10], let-7g [19], miR-125a-5p [10, 31], miR-125b [31] and miR-126 [40] have been described as downregulated. [score:4]
Previous studies have demonstrated that there is a large number of deregulated miRNAs in human breast cancer (in particular, miR-10b, miR-17-5p, miR-21, miR-27a, miR-27b, miR-125a, miR-125b, miR-126, miR-145, miR-155, miR-200c, miR-206, miR-336 and the let-7 family) [9- 31]. [score:2]
According to previous reports in female breast carcinogenesis, the most interesting and promising miRNAs of this male breast cancer signature are miR-10b, miR-126, miR-125a-5p and miR-125b [14, 31, 40]. [score:1]
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[+] score: 23
The reconstitution of TFF1 expression significantly reduced miR-504 expression, but not miR-125, in AGS (A) and STKM2 (B) cells; the levels of TFF1 mRNA expression are shown. [score:7]
To test this hypothesis, we first checked the microRNA expression of miR-125 and miR-504 in response to TFF1 expression. [score:5]
The quantitative real time PCR data showed that the reconstitution of TFF1 expression significantly decreased miR-504 levels, but not miR-125, in AGS (p<0.05, Figure 4A) and STKM2 (p<0.01, Figure 4B) cells, suggesting that. [score:3]
Recent studies showed that some microRNAs, such as miR-504 and miR-125, may directly regulate p53 by reducing its protein levels [28, 34, 35]. [score:3]
Protein levels and function of p53 have been shown to be regulated by miRNAs including miR-125 [43], miR-18 [23], and miR-504 [28]. [score:2]
Figure 4 AGS and STKM2 cells were transiently transfected with PTT5 empty vector or TFF1 and subjected to quantitative real-time PCR of mature miR-125, miR-504, and TFF1 48 hours post transfection. [score:1]
The miRNA levels of endogenous mature miR-125 and miR-504 were analyzed and normalized with miR-191. [score:1]
AGS and STKM2 cells were transiently transfected with PTT5 empty vector or TFF1 and subjected to quantitative real-time PCR of mature miR-125, miR-504, and TFF1 48 hours post transfection. [score:1]
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[+] score: 23
Sybr Green technology was used to validate: miR-122, which was specifically expressed on present microarrays compared to our previous study [11] and it showed the highest up-regulation; miR-21 and miR-126, which are in addition to muscle-specific miR-1 and miR-133 the most common miRNAs involved in heart diseases; miR-125a/b, which are according to TAM tool involved in myocardial remo delling after MI. [score:7]
We also showed down-regulation of miR-126, which plays an important role in ischemic angiogenesis [40], miR-125a/b, which are involved (according to TAM) in myocardial remo delling after MI, although their target genes in cardiovascular pathology are not known at the present. [score:6]
Free-energy of binding and flanking regions (RNA22, RNAfold) was calculated for 10 up-regulated miRNAs from microarray analysis (miR-122, miR-320a/b/c/d, miR-574-3p/-5p, miR-199a, miR-140, and miR-483), and nine miRNAs deregulated from microarray analysis were used for validation with qPCR (miR -21, miR-122, miR-126, miR-1, miR-133, miR-125a/b, and miR-98). [score:3]
Expression of miRNAs (miR-21, miR-125a/b, miR-122 and miR-126) is dependent of RG and type of tissue. [score:3]
The same is true for expression of miR-125a-5p and miR-125b. [score:3]
MicroRNAs, miR-122, miR-125a-5p, miR-125b, miR-126, miR-21 were tested relatively to RNU6B and miR-26b. [score:1]
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[+] score: 22
Twelve of them (miR-10b, miR-15a, miR-19a, miR-26b, miR-30a, miR-30c, miR-125a, miR-125b, miR-148a, miR-148b, miR-195 and miR-320) are down-regulated both in dogs and in humans whereas one (miR-494) is up-regulated in both species and four (miR-29a, miR-181a, miR-196a and miR-374a) are down-regulated in dogs but up-regulated in humans. [score:13]
We also found the significant down-regulation of miR-29b, miR-101, miR-143, miR-145 and miR-125a in a metastatic group in comparison with benign tumours. [score:4]
They also found that miR-29b, miR-101, miR-143, miR-145 and miR-125a are down-regulated in metastatic sites when compared to the primary tumours. [score:3]
Von Deetzen et al. compared the expression profiles of 16 microRNAs (miR-136, miR-143, let-7f, miR-29b, miR-145, miR-9, miR-10b, miR-203, miR-125b, miR-15a, miR-16, miR-21, miR-101, miR-210, miR-194 and miR-125a) in three types of canine mammary tumours (adenoma, non-metastasising carcinoma, metastasising carcinoma), lymph node metastases and in a normal mammary gland. [score:2]
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[+] score: 21
In order to further understand the role of aberrant miRNAs in physiological functions and biologic processes in arsenite -induced neoplastic transformation cells, 11 downregulated miRNAs (miR-197-3p, miR-192-5p, miR-127-3p, miR-139-5p, miR-490-3p, miR-196b-5p, miR-125a-3p, miR-298, miR-542-3p, miR-15b-5p, and miR-33b-5p) and six upregulated miRNAs (miR-200b-3p, miR-106b-5p, miR-574-5p, miR-320d, miR-200c-3p, and miR-141-3p) (Table S2) were selected, and their target genes were predicted with the TargetMiner, miRDB, and TarBase databases. [score:11]
Among the 191 dysregulated miRNAs, seventeen miRNAs (downregulation miRNAs: miR-197-3p, miR-192-5p, miR-127-3p, miR-139-5p, miR-490-3p, miR-196b-5p, miR-125a-3p, miR-298, miR-542-3p, miR-15b-5p, miR-33b-5p; upregulation miRNAs: miR-200b-3p, miR-106b-5p, miR-574-5p, miR-320d, miR-200c-3p, miR-141-3p, Table S2) were selected for bioinformatics analysis. [score:8]
Furthermore, the miRNA profile of the arsenite -induced neoplastic transformation in our study showed that a series of miRNAs is often dysregulated in lung cancer, e. g., let-7 family, miR-200 family, miR-125a, miR-145, miR-192, miR-145, miR-335 [36]. [score:2]
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[+] score: 21
In fact, growing evidence of indirect p53 deregulation in MM through MDM2 overexpression, TP53 promoter hypermethylation and alterations in certain miRNAs that directly or indirectly affect p53 expression, such as miR-25, miR-30d, miR-125a-5p and miR-214, have been reported. [score:9]
Leotta M. Biamonte L. Raimondi L. Ronchetti D. di Martino M. T. Botta C. Leone E. Pitari M. R. Neri A. Giordano A. A p53 -dependent tumor suppressor network is induced by selective miR-125a-5p inhibition in multiple myeloma cells J. Cell. [score:5]
The miR-125a-5p which has been described to be upregulated in a subset of MM patients carrying the t(4;14) translocation [108], directly binds to TP53 mRNA 3′-UTR triggering a decrease of p53 levels. [score:5]
Similarly, other microRNAs such as miR-125b, miR-125a and miR-1285 have been described as negative regulator of TP53 [104, 105, 106]. [score:2]
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[+] score: 21
More importantly, the miRNAs analyzed in this study not only included the miRNAs like Let-7a, miR-15b, miR24, miR-100 and miR-125 which may suppress the expression of cyclins A and B, and miRNAs such as Let-7a, miR24 and miR-125 which may regulate activity of CDK1, but also miRNAs such as miR-181a, miR-221 and miR-222 which can target CDK inhibitors [30– 32]. [score:10]
To investigate whether miRNAs have a role in the cell cycle regulation of splenocytes following aniline exposure, the expression of miRNAs, including Let-7a, miR-15b, miR24, miR-100, miR-125, miR-181a, miR-221 and miR-222 which are known to mainly control G2/M phase regulators [30– 32], was analyzed by using real-time PCR and the results are presented in Fig 7. Aniline exposure led to significantly decreased expression of Let-7a (decreased 82%), miR-15b (decreased 62%), miR24 (decreased 78%), miR-100 (decreased 63%), miR-125 (decreased 86%), whereas miR-181a, miR-221 and miR-222 increased by 155%, 78% and 56%, respectively, in comparison to controls (Fig 7). [score:5]
Real-time PCR analysis of miRNAs Let-7a, miR-15b, miR24, miR-100 and miR-125 (A), and miRNAs miR-181a, miR-221 and miR-222 (B) expression in rat spleens following aniline exposure. [score:3]
Therefore, greater decreases in Let-7a, miR-15b, miR24, miR-100 and miR-125 expression and significant increases in miR-181a, miR-221 and miR-222 levels in the spleens following aniline treatment may be mechanistically important in generalizing that aniline exposure leads to increased cyclin A, cyclin B, CDK1, and decreased p21, p27, thus triggering the splenocytes to go through G2/M transition. [score:3]
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[+] score: 21
miR-125a-3p inhibits autophagy through targeting UV radiation resistance -associated gene (UVRAG), miR-33 targets ATG5/LAMP1, miR-144-3p targets autophagy-related gene 4a (ATG4a), miR-23a-5p inhibits the TLR2/MyD88/NF-κB leading to reduced autophagy and miR-33 also plays an inhibitory role via targeting some unknown factors. [score:15]
miR-125a-3p, miR-33, miR-144-3p, miR-23a-5p, and miR-142-3p are potential inhibitors of autophagy in Mycobacterium tuberculosis (Mtb) infection. [score:3]
MicroRNA-125a inhibits autophagy activation and antimicrobial responses during mycobacterial infection. [score:2]
1 and primary human macrophages Bettencourt et al., 2013 miR-33 ATG5, LAMP1 Human THP-1 and HEK293 cells Ouimet et al., 2016 miR-125a-3p UVRAG Mouse RAW264.7 and J774A. [score:1]
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[+] score: 20
TRAF6 was identified as one of the direct targets for miR-125a and after activation by NF-κβ, NFATc1 binds to miR-125a promoter to inhibit TRAF6 [40]. [score:6]
The microRNA hsa-miR-125a-5p in this study identified to have fifteen targets which include the well-known targets NF-κβ, SP1, and MMP2. [score:5]
The miR-125a-5p has been reported to be downregulated in male breast cancer patients with respect to tumor ErbB2 levels [40, 41]. [score:4]
Furthermore, hsa-miR-125a-5p downregulates HBV (hepatitis B virus) surface antigen and arrests secretion of HBsAg. [score:4]
The extrapolation of hsa-miR-125a-5p to human tendon tissues can pave way for the elucidation of their functional role in tendinopathies. [score:1]
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[+] score: 20
The miR expression profile of E. granulosus was studied for its different developmental stages and the protoscolex and cyst wall both showed the expression of miR-2, miR-9, miR-10, miR-27, let-7, and miR-71 except for miR-125 which was present only on protoscolex (Cucher et al., 2011). [score:6]
These miRs are involved in metamorphosis of parasite along with let-2. The protoscolex of E. granulosus had higher expression of miR-2 and miR-125 and their sequence showed variability, suggesting that it is due to binding to various 3′UTR targets. [score:5]
These studies had shown that the activation of TIRs and TNF-α receptor results in rapid expression of a host of miRNAs including let-7, miR-9, miR-99b, let-7e, miR-125a, miR-132, miR- 146a, miR-146b, miR-155, miR-187, and miR-223 (Taganov et al., 2006; Tili et al., 2007; Bazzoni et al., 2009; Ceppi et al., 2009). [score:3]
Human mir-125 family members have been previously identified as decisive players in immune system development, immunological host defense and in cancer (Sun et al., 2013). [score:2]
The miR-125 and miR-2 in the storbilated stage suggests their role in correct sexual development via notch signaling (miR-125). [score:2]
They found fhe-mir-125b as most abundant miRNA in EV; this miR belongs to the eumetazoan mir-10 family and has three orthologs in the host (cattle; Bos taurus; bta-mir-125a, bta-mir-125-1/-2b). [score:1]
Diverse functions of miR-125 family in different cell contexts. [score:1]
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51
[+] score: 20
MiRNA families such as miR-200 (cfa-miR-200a, cfa-miR-200b and cfa-miR-200c), Mirlet-7 (cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa-let-7g and cfa-let-7f), miR-125 (cfa-miR-125a and cfa-miR-125b), miR-146 (cfa-miR-146a and cfa-miR-146b), miR-34 (cfa-miR-34a, cfa-miR-34b and cfa-miR-34c), miR-23 (cfa-miR-23a and cfa-miR-23b), cfa-miR-184, cfa-miR-214 and cfa-miR-141 were significantly up-regulated with testicular RA intervention via administration of CYP26B1 inhibitor and all-trans-RA (Figure 5). [score:6]
Up-regulated miRNAs (cfa-let-7, cfa-miR-200, cfa-miR-125, cfa-miR-34, cfa-miR-23, cfa-miR-146 clusters, cfa-miR-184 and cfa-miR-214) in adult canine testis treated with DMSO, RA or CYP26B1 inhibitor. [score:6]
Target genes and their biological functions for miR-34 and miR-125 clusters are given in Table S2. [score:3]
Among dysregulated miRNAs in this study, an association network was created for let-7, miR-200, miR-34 and miR-125 families. [score:2]
0099433.g007 Figure 7 Let-7, miR-200, miR-34 and miR-125 clusters are chosen to create networks. [score:1]
Let-7, miR-200, miR-34 and miR-125 clusters are chosen to create networks. [score:1]
Table S2 Associated genes and their biological function for miR34 and miR125 clusters (with references). [score:1]
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52
[+] score: 19
While miR-1290 and miR-572 were found to be upregulated, miR-125a-3p, miR-134, miR-584-5p, miR-663a, and miR-513a-5p were determined to be downregulated in various types of cancer [48– 64]. [score:7]
According to Kumar and Nerurkar miR-125a-3p target multiple genes involving production of cytokines, chemokines, and expression of apoptotic genes, which belong to different signaling pathways that play a critical role in West Nile virus neuropathogenesis [66]. [score:5]
Among these miRNAs, miR-134 and miR-125a-3p have been linked to infectious diseases. [score:3]
Additionally, the expression level of miR-125a-3p was determined in higher levels in HIV (+) samples than in healthy controls [67]. [score:3]
Schnitger et al. demonstrated that miR-125a-3p take part in the early innate immune response of macrophages to Listeria infection [65]. [score:1]
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53
[+] score: 19
Study demonstrated that either miR-125a or miR-125b can suppress the expression of HER2 and HER3 [25]; two important tyrosine kinase receptors frequently deregulated in breast cancer. [score:6]
The previous findings that miR-206 regulated ER α expression in breast cancer [22] support the suggestion that miR-206 could be a novel candidate for endocrine therapy to specifically target ER α. Since miR-125a/b was another miRNA involved in HER family -mediated pathway [25], such miRNA could be another target to investigate the mechanism of action of Trastuzumab to the perturbation of signaling pathway in cancer cells. [score:6]
miR-125a and -b were downregulated in breast cancer [9]. [score:4]
Restoration of miR-125a/b impaired tumor cell growth and reduced tumor cell migration and invasion, suggesting a therapeutic use of miRNAs in tumor suppression. [score:3]
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54
[+] score: 19
miR-125-5p inhibited TP53 expression. [score:5]
CUR inhibited the expression of miR-125-5p, miR-574-3p and miR-210 in undifferentiated nasopharyngeal carcinoma (NPC). [score:5]
CUR was determined to inhibit miR-125-5p but increase TP53 expression [175]. [score:5]
In contrast, forced expression of miR-125-5p stimulated proliferation, migration and invasion of HONE1 cells. [score:3]
miR-125-5p was determined to be detected at higher levels in NPC than in healthy controls. [score:1]
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55
[+] score: 19
There are upregulation of miR-155, miR-146, miR-132, miR-147, miR-9, miR-21, miR-223, miR-125b, miR-27b, let-7e and down-regulation of miR-125, let-7i, miR-98 following TLR4 stimulation [22, 23, 28– 35]. [score:7]
Previous studies have shown that miR-155, miR-146a, miR-146b, miR-125a and miR-455 can be up-regulated by heat killed C. albicans in Bone marrow derived macrophages [21]. [score:4]
Monk et al. reported that miR-455, miR-125, miR-146 and miR-155 were up-regulated in murine bone marrow derived macrophages (BMDMs) stimulated with heat killed C. albicans [21]. [score:4]
However, in contrast to their results, the up-regulation of miR-455, miR-125 and miR-155 was not be detected in our study. [score:4]
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56
[+] score: 19
An increase of miR-30c and miR-31 miRNAs, targeting osteogenic transcripts such as RUNX2 and Osterix, [23, 26- 28] and of miR-125a known to be significantly downregulated during osteogenic differentiation in human adipose-derived stem cells [38] and predicted to target the osteogenic genes Smad 2 and 4 [39], could be found in hOst incubated with hAdi-CM. [score:8]
Five miRNAs, miR-138, miR-30c, miR-125a, miR-125b and miR-31, were selected for their capacity to inhibit osteoblast gene expression [25- 28]. [score:5]
We observed in the osteoblastic population an increase in the adipogenic PPARγ, leptin, CEBPα and CEBPδ transcripts, dependent on mRNA amount as shown by conditioned media obtained from adipocytes at several differentiation stages and PPARγ silencing experiments, as well as the anti-osteoblastic miR-138, miR30c, miR125a, miR-125b, miR-31 miRNAs [23- 26], probably implicated in osteocalcin (OC) and osteopontin (OP) expression decrease. [score:3]
We observed in hMSC-Ost incubated in hAdi-CM an increase in the adipogenic PPARγ, leptin, CEBPα and CEBPδ transcripts as well as the anti-osteoblastic miR-138, miR30c, miR125a, miR-125b, miR-31 miRNAs, probably implicated in the observed osteocalcin (OC) and osteopontin (OP) expression decrease. [score:3]
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57
[+] score: 18
Moreover, miR-125a-5p inhibits LIN28A; LIN28A in turn inhibits hsa-let-7c-5p biogenesis 29– 31, which could indirectly contribute to the rise of let-7c-5p we have observed. [score:6]
LIN28A has a role in tissue repair [32], which would be diminished upon upregulation of miR-125a-5p. [score:4]
miR-99b-5p and miR-125a-5p both belong to the same cluster and are known to be expressed in endothelial cells [26]. [score:3]
Based on inspection of the volcano plots and an in silico analysis of regulated pathways with DIANA miRPath v. 2.0 [10] we chose a set of 16 miRNAs for confirmation in microdissected glomeruli from patients with only HLA-class I DSAs: miR-let-7c, miR-28-3p, miR-29b, miR-30d, miR-99b, miR-125a-5p, miR-133a, miR-138, miR-146b, miR-195, miR-374b-3p, miR-484, miR-501-3p, miR-520e, miR-625-3p, miR-885-5p (Table  1). [score:2]
0.09; 0.04; 0.10; p < 0.001), miR-125a-5p (2.72; 1.46; 5.14 vs. [score:1]
The top three miRNAs which contributed the most to the classification performance were miR-125a-5p, let-7c-5p, and miR-99b-5p. [score:1]
Glomerular miR-let-7c-5p (a), miR-28-3p (b), miR-30d-5p (d), miR-99b-5p (e), miR-125a-5p (f) and miR-195-5p (j), miR-374b-3p (k), miR-484 (l), miR-501-3p (m), miR-520e (n) and miR-885-5p (p) were higher in DSA+ than to controls. [score:1]
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58
[+] score: 18
Bi Q Tang S Xia L Du R Fan R Gao L Jin J Liang S Chen Z Xu G Nie Y Wu K Liu J Shi Y Ding J Fan D Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGFPLoS One. [score:6]
Notably the microRNAs upregulated in the control fascia accounting for the greatest differential in read count are heavily enriched in previously validated anti-fibrotic extracellular matrix targeting microRNAs (Table  1), including let-7 [23– 25], miR-29a-3p [26], miR-26b-5p, miR-30d-5p [27, 28], miR-27a-3p, miR-27b-3p [29, 30], miR-10a-5p [31], miR-26a-5p [32– 35], miR-101-3p [36– 39], and miR-10b-5p [40], as well as anti-proliferative microRNAs including, miR-126-3p [41– 47], miR-99a-5p [48– 54], miR-125a-5p [55– 59], and miR-139-5p [60– 62]. [score:6]
Additional enriched microRNAs (miR-126-3p [46– 52], miR-99a-5p [53– 59], miR-125a-5p [60– 64], and miR-139-5p [65– 67]) have been shown to affect proliferation in cancer, and may regulate the fibroproliferative activity seen in Dupuytren’s disease. [score:4]
Tiwari A Shivananda S Gopinath KS Kumar A MicroRNA-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor α: implications for cancer therapeuticsJ Biol Chem. [score:2]
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59
[+] score: 18
The expression of miRNAs in epithelial cells was similar to that in whole lung and included miR-125a, miR-30b/c/d, miR-20d, miR-93 and miR-26b, although some of the miRNAs were also significantly expressed in macrophages and fibroblasts (e. g. miR-30c). [score:5]
Expression profiling of human airway biopsies revealed several highly expressed miRNAs, including miR-92, miR-200c, miR-26a, miR-16, let-7b, miR-125a and miR-125b, which together comprised 55.5% of the total miRNA species analysed. [score:5]
This analysis revealed that miR-92, miR-26a, miR-200c, miR-16, let-7b, miR-125a, and miR-125b were the most highly expressed in human airway tissue, having levels more than 70-fold higher than the average miRNA and contributing 55.5% of the total mRNA detected in airway biopsies. [score:3]
The rate of apoptosis or proliferation is known to be regulated by miR-16 and let-7 [23], [44] whilst miR-125 is the mammalian homologue of lin-4, and has previously been shown to be associated with embryonic development [45]. [score:3]
In addition, members of the let-7 family (let-7a, let-7b and let-7c), miR-26 family (miR-26a and miR-26b), miR-125 family (miR-125a and miR-125b) and miR-30 family (miR-30a-5p, miR-30b and miR-30c) also fell within the highly expressed category and are therefore considered to be human airway specific (figure 4). [score:2]
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60
[+] score: 18
LEP also has a target site for miR-125a, which is downregulated in obese adipose tissue, an observation in agreement with human studies [41]. [score:6]
MiR-9-5p, miR-148a and miR-125a also have target sites in SCD, which is upregulated in the adipose tissue of the obese minipigs. [score:6]
LEP was the gene containing the most miRNA target sites, i. e. is targeted by miR-148a-3p, miR-125a-5p, miR-30a, miR-9-5p and miR-17-5p. [score:5]
In addition, miR-30a, miR-125a and miR-148a all had fold changes of < -1.5 and p values < 0.05. [score:1]
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61
[+] score: 17
By the end of the year 2010, miR-199a-3p and miR-210 were found to suppress HBsAg expression by directly targeting the HBV S protein coding region and pre-S1 region, respectively [37]; miR125a-5p was then shown to interfere with the viral translation, down -regulating the expression of the surface antigen [38], while miR-1 increases HBV transcription by upregulating farnesoid X receptor α (FXRA), a nuclear receptors binding to the HBV core promoter and regulating HBV transcription and replication. [score:17]
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62
[+] score: 16
The restoration of miR-205 has been shown to restrain cell viability via targeting MED1, miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells, miR -23b represses proto-oncogene Src kinase, miR-125a and miR-125b suppress the oncogenes ERBB2 and ERBB3 [14– 17]. [score:9]
Meanwhile, several miRNAs were also shown to be deregulated and functionally relevant across different cancer diseases: down-regulation of miR-125a and miR-125b in breast cancer [9], the let-7 miRNAs in lung cancer [10], and miR-143 and miR-145 in different cancer types [11]. [score:7]
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63
[+] score: 16
[16] MicroRNAs including miR-125a [17] and members of the let-7 family 18, 19 have been shown to be significantly downregulated in NSCLC tumor samples, with low levels of expression associated with poor clinical outcomes. [score:6]
To determine whether serum levels of representative microRNAs were PPB-specific or indicative only of changes due to germline DICER1 mutations, we compared the findings for the two highest ranking differentially expressed microRNAs (miR-125a-3p and miR-125b-2-3p) with levels from two family members (mother and maternal grandmother) known to harbor the same germline DICER1 mutation that was detected in the patient (Figure 2d). [score:4]
Finally, using linear regression, we showed that levels of miR-125a-3p and miR-125b-2-3p were highly correlated (P=0.0002) (Figure 2d, right panel), suggesting that changes in the levels of these two independently transcribed microRNAs (Table 1) were disease -associated. [score:3]
16, 17, 18, 19, 20, 21 The six top-ranking microRNAs from our subset of 10 (miR-125a-3p, miR-125b-2-3p, miR-380-5p, miR-125b-1-3p, let-7f-2-3p and let-7a-3p) are represented graphically in Figure 2c. [score:1]
We next analyzed serum levels of miR-125a-3p and miR-125b-2-3p at the four time-points from which serum was available in the PPB case, representing two time-points before the delivery of chemotherapy (i. e. during diagnostic work-up), and two following. [score:1]
The most substantial increase was for miR-125a-3p, with levels over 40- and 33-fold higher than the control group and the ‘other tumor' group, respectively. [score:1]
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64
[+] score: 15
This study confirmed that underexpression of miR-125a contributes to the elevated expression of RANTES in SLE, increasing T cell recruitment to inflammatory tissues [65]. [score:5]
miR-125a has binding sites in the 3′ UTR of KLF13, which belongs to the family of transcription factors that regulates the expression of the inflammatory chemokine RANTES (CCL5) in T cells. [score:4]
An additional study examining PBMC miRNAs found that decreased miR-125a expression in SLE patients contributed to increased KLF13 production by T cells. [score:3]
Increasing miR-125a levels in T cells from SLE patients ex vivo alleviated elevated RANTES expression. [score:3]
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65
[+] score: 15
In the present study, we showed that the expression of several miRNAs is altered during the development of PC and that licofelone reverses the altered expression of the majority of these miRNAs with up-regulation of miR-21, miR-222, Let-7, miR-125, miR-142 and down-regulation of miR-1, miR-122 and miR-148. [score:12]
For example, Lee EJ 2007 et al. [44] showed that the miRNAs miR155, miR21, miR222, Let7, miR376a, miR301, miR100, miR125, miR142 and others are overexpressed significantly in human PC. [score:3]
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66
[+] score: 15
MiRNA subtypes, including miR-548d-3p, miR-559, miR-125a, miR-125b, miR-205, miR-155 and miR-4728, target ERBB2 and are downregulated in cancers [17– 20]. [score:6]
Consequently, the expression of ERBB2 in miR-3622b-5p -transfected cells, not in cells transfected with miR-18-5p, miR-125-5p or miR-133a-3p, was more significantly depressed than that in control cells (Figure 1A and Supplementary Figure 1). [score:3]
org) suspects that ERBB2 is the target gene of the miR-18-5p, miR-125-5p, miR-133a-3p or miR-3622b-5p. [score:3]
To explore whether ERBB2 is the target gene of those miRNAs, we transfected miR-18-5p, miR-125-5p, miR-133a-3p or miR-3622b-5p mimic and miRNA mimic control into SK-BR-3 or SNU-216 cells. [score:3]
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67
[+] score: 15
mRNA, messenger RNA Table 1circRNA-miRNA-mRNA network elements for those circRNA-miRNA interactions predicted by both miRanda and RNAHybrid, with a miRanda match score > = 180 and mRNA targets that are differentially expressed (uncorrected P < 0.05) with log2(fold change) >= 2 or =< − 2 (high stringency network) Circular RNA microRNA target Number of binding sites predicted Target genes (differentially expressed) X:47,431,299–48,327,824 hsa-miR-139-5p 6 NOTCH1, STAMBP, TPD52 8:144,989,320–145,838,888 hsa-miR-320a 2 METTL7A, PBX3, PLS1, SEC14L1, VCL, VIM, VOPP1, YPEL2 8:144,989,320–145,838,888 hsa-miR-320b 2 RTKN, VCL, VOPP1 X:47,431,299–48,327,824 hsa-miR-449a 1 BAZ2A, MFSD8, NOTCH1, TSN, ZNF551 8:144,989,320–145,838,888 hsa-miR-125a-3p 1 ANKRD62, C15orf40, COL18A1, MFSD11, MPEG1, MUL1, TTC31, WDR12, ZNF641 X:47,431,299–48,327,824 hsa-miR-125a-5p 1 CD34, MEGF9, PANX1, RIT1, TP53INP1 8:144,989,320–145,838,888 hsa-miR-125a-5p 1 CD34, MEGF9, PANX1, RIT1, TP53INP1 X:47,431,299–48,327,824 hsa-miR-324-5p 1 FOXO1, MEMO1, PSMD4, SMARCD2 14:23,815,526–24,037,279 hsa-miR-142-3p 1 BTBD7, CLDN12, CPEB2, CSRP2, DAG1, KIF5B, PTPN23, WHAMM 4:88,394,487–89,061,166 hsa-miR-133b 1 FAM160B1 4:88,394,487–89,061,166 hsa-miR-448 1 DDIT4, PURG 4:88,394,487–89,061,166 hsa-miR-339-5p 1 AXL, HLA-E, METTL7A, ZNF285, ZNRF3 MetaCore pathway analysis on the 255 filtered differentially expressed target genes from the previous analysis revealed 112 perturbed pathways (corrected P < 0.01; Table  2, Additional file  8: Table S5). [score:15]
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[+] score: 15
The miR-125a-5p-regulated PIN was found to be able to inhibit apoptosis and regulate epithelial cell proliferation, and has been reported to repress cell growth [36]. [score:5]
For example, the nerve growth factor receptor pathway was enriched in miR-regulated PINs of miR-520d-3p, miR-497-5p, miR-125a-5p, miR-125b-5p, and miR-31-5p, and the epidermal growth factor receptor pathway was enriched in miR-regulated PINs of miR-520d-3p, miR-21-5p, and miR-497-5p. [score:3]
Further, miR-125b [18], and miR-145 [19] were identified as tumor suppressors in breast cancer, and miR-125a was found to repress tumor growth in breast cancer [20]. [score:3]
Also, the enriched term “regulation of epithelial cell proliferation” for both miR-125a-5p and miR-125b-5p were found to be associated with the 10-year survival rate of patients. [score:2]
We noted that 7 miRNAs had enriched GO terms related to apoptosis, cell death, and cell proliferation, i. e., miR-520d-3p, miR-497-5p, miR-125b-5p, miR-21-5p, miR-31-5p, let-7c, and miR-125-5p. [score:1]
Here, some previously known functions of miRNAs were again presented in our results, e. g., the relationship between the miRNAs, let-7c, miR-125a-5p, miR-125b-5p, and miR-21-5p, and breast cancer were demonstrated in this research. [score:1]
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69
[+] score: 14
Decreased expression of microRNA-125a-5p is associated with cell dedifferentiation [50] and in human embryonic stem cells antagonizing microRNA-125a-5p inhibits cell differentiation and upregulates pluripotency markers [51]. [score:8]
Both of these microRNAs as well as microRNA-125a-5p (which was also significantly decreased with simulated microgravity) are downregulated during skin wound-healing [47]. [score:4]
MicroRNA-125a-5p represses the expression of pro-regenerative proteins such as Lin28[48]. [score:2]
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70
[+] score: 14
miR-125, miR-302, and miR-371 both target proteins involved directly in signaling mediated by receptors of the TGF-beta family and modulate finely the strength of the signal transduction. [score:4]
Using this mo del, the kinetics of activation of three brain-expressed miRNAs, miR-9, miR-124, and miR-125, was analyzed over time. [score:3]
miR-125 was also reported as a key regulator of hESC neural conversion. [score:2]
Functional studies confirmed that miR-125 activity was necessary to fully achieve an efficient engagement of hESC into the neural lineage by both promoting hESC differentiation and blocking alternative, non-neural fate choices. [score:1]
Silencing by miR-125 of Smad-4, the key co-factor of activin- and BMP -dependent Smad pathways, was central to its role in the promotion on neural commitment. [score:1]
At least two miRNAs have been demonstrated to promote the conversion of PSCs into neuro-epithelial cells, miR-125 and miR-145. [score:1]
miR-125 potentiates early neural specification of human embryonic stem cells. [score:1]
Only miR-125 was found to be activated in a time window compatible with a role in the neural commitment decision. [score:1]
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71
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Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro -RNA miR-125a or. [score:5]
Sirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors miR-125a-5p and. [score:4]
MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells. [score:4]
Comprehensive microRNA analysis identifies and miR-125a-5p as plasma biomarkers for rheumatoid arthritis. [score:1]
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72
[+] score: 14
The miR-125a has been reported to be a tumour suppressor in malignancies of gastric cancer and to suppress the proliferation of gastric cancer cells in combination with trastuzumab, a monoclonal antibody against ERBB2 (Ref. [score:5]
Clinicopathological characteristic miRNAs Overall survival and recurrence: miR-10b, miR-21*, miR-214*, miR-335*, miR-375(78, 94, 121, 122, 123, 124, 125, 126, 127, 128) Tumor-suppressor-miRs: Let-7a*, Let-7 g*, miR-125a*, miR-126, miR-146a, miR-142-5p, miR-223, miR-338, miR-433 *miRNAs are also reported to be aberrantly expressed in human ovarian cancer. [score:3]
Low expression levels of miR-125a and miR-146a were unfavourable prognostic factor of overall survival (Refs 78, 123). [score:3]
PLoS ONE 6, e25872 78 Nishida N. (2011) MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. [score:2]
Conversely, low levels of miR-125a and miR146a correlated significantly with lymph node metastasis (Refs 78, 123). [score:1]
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73
[+] score: 14
In addition, many miRNAs have been noted to be differentially expressed in SLE patients versus healthy controls, and miR125a, a member of the family responsible for down-regulation of Bright activity in B cell progenitors (61), was described as being down-regulated in lupus lymphocytes [reviewed in Ref. [score:9]
Previous studies characterized expression of the miR125 family of micro RNAs in human B lymphocytes at various stages of differentiation, showing members of this family were differentially expressed according to the maturation state of the cells (60). [score:3]
An important microRNA family regulating transcript levels during hematopoiesis is miRNA125. [score:2]
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74
[+] score: 14
In turn, in our study, SIRT7 targeting miR-125a was under-expressed in obese individuals and this finding was consistent with animal studies where down-regulation of this miRNA in murine adipocytes was associated with insulin resistance [88]. [score:8]
As mentioned above, SIRT -targeting miRNAs were found to be crucial for the regulation of adipogenesis and determination of MSCs differentiation towards preadipocytes (e. g., miR-34a, miR-22, miR-93, miR-146b, miR-181a) as well as lipid metabolism (miR-33, miR-34a), insulin secretion (miR-15b) and sensitivity (miR-125a), and their expression profile differs between tissues obtained from obese and normal-weight individuals [26, 41, 44, 53, 85, 86, 87, 88]. [score:6]
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75
[+] score: 14
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-130a, mmu-mir-138-2, mmu-mir-181a-2, mmu-mir-182, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-10a, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-181a-1, mmu-mir-297a-1, mmu-mir-297a-2, mmu-mir-301a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-106a, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-138-2, hsa-mir-125b-2, hsa-mir-138-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-34a, rno-mir-301a, rno-let-7d, rno-mir-344a-1, mmu-mir-344-1, rno-mir-346, mmu-mir-346, rno-mir-352, hsa-mir-181b-2, mmu-mir-10a, mmu-mir-181a-1, mmu-mir-29b-2, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-125b-1, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-30e, hsa-mir-362, mmu-mir-362, hsa-mir-369, hsa-mir-374a, mmu-mir-181b-2, hsa-mir-346, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-10a, rno-mir-15b, rno-mir-26b, rno-mir-29b-2, rno-mir-29a, rno-mir-29b-1, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-34b, rno-mir-34c, rno-mir-34a, rno-mir-106b, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-130a, rno-mir-138-2, rno-mir-138-1, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-181a-1, hsa-mir-449a, mmu-mir-449a, rno-mir-449a, mmu-mir-463, mmu-mir-466a, hsa-mir-483, hsa-mir-493, hsa-mir-181d, hsa-mir-499a, hsa-mir-504, mmu-mir-483, rno-mir-483, mmu-mir-369, rno-mir-493, rno-mir-369, rno-mir-374, hsa-mir-579, hsa-mir-582, hsa-mir-615, hsa-mir-652, hsa-mir-449b, rno-mir-499, hsa-mir-767, hsa-mir-449c, hsa-mir-762, mmu-mir-301b, mmu-mir-374b, mmu-mir-762, mmu-mir-344d-3, mmu-mir-344d-1, mmu-mir-673, mmu-mir-344d-2, mmu-mir-449c, mmu-mir-692-1, mmu-mir-692-2, mmu-mir-669b, mmu-mir-499, mmu-mir-652, mmu-mir-615, mmu-mir-804, mmu-mir-181d, mmu-mir-879, mmu-mir-297a-3, mmu-mir-297a-4, mmu-mir-344-2, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, mmu-mir-466c-1, mmu-mir-466e, mmu-mir-466f-1, mmu-mir-466f-2, mmu-mir-466f-3, mmu-mir-466g, mmu-mir-466h, mmu-mir-493, mmu-mir-504, mmu-mir-466d, mmu-mir-449b, hsa-mir-374b, hsa-mir-301b, rno-mir-466b-1, rno-mir-466b-2, rno-mir-466c, rno-mir-879, mmu-mir-582, rno-mir-181d, rno-mir-182, rno-mir-301b, rno-mir-463, rno-mir-673, rno-mir-652, mmu-mir-466l, mmu-mir-669k, mmu-mir-466i, mmu-mir-669i, mmu-mir-669h, mmu-mir-466f-4, mmu-mir-466k, mmu-mir-466j, mmu-mir-1193, mmu-mir-767, rno-mir-362, rno-mir-504, rno-mir-582, rno-mir-615, mmu-mir-3080, mmu-mir-466m, mmu-mir-466o, mmu-mir-466c-2, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466p, mmu-mir-466n, mmu-mir-344e, mmu-mir-344b, mmu-mir-344c, mmu-mir-344g, mmu-mir-344f, mmu-mir-374c, mmu-mir-466b-8, hsa-mir-466, hsa-mir-1193, rno-mir-449c, rno-mir-344b-2, rno-mir-466d, rno-mir-344a-2, rno-mir-1193, rno-mir-344b-1, hsa-mir-374c, hsa-mir-499b, mmu-mir-466q, mmu-mir-344h-1, mmu-mir-344h-2, mmu-mir-344i, rno-mir-344i, rno-mir-344g, mmu-let-7j, mmu-mir-30f, mmu-let-7k, mmu-mir-692-3, rno-let-7g, rno-mir-15a, rno-mir-762, mmu-mir-466c-3, rno-mir-29c-2, rno-mir-29b-3, rno-mir-344b-3, rno-mir-466b-3, rno-mir-466b-4
The relative expression intensities of miR-125 were 2.8 ± 1.6 in adenoma-free mice and 5.6 ± 2.7 in adenoma-bearing mice, thus accounting for a 2.0-fold upregulation. [score:6]
Our study showed that no miRNA was different between males and females in adenoma-free mice, while 3 miRNAs (miR-10a, miR-125, and miR-130a) were differentially expressed in adenoma-bearing male and female mice. [score:3]
The panels report the amplification curves for each one of the 20 mouse lung fragments tested, either adenoma-free (green) or adenoma-bearing (purple), relatively to miRNAs miR-125, miR-374, and miR-669k. [score:1]
According to volcano-plot analyses, no miRNA was different in males and females from adenoma-free mice, whereas 3 miRNAs (miR-10a, miR-125, and miR- 130a) from adenoma-bearing mice showed intergender differences. [score:1]
In particular, miR-10a is related to estrogen dependent cancer promotion [112, 113], miR-130a both to the estrogen and HER2 pathways [114, 115], and miR-125 to HER2/erbb2 estrogen sensitive oncogene activation [116, 117]. [score:1]
Validation of microarray data was performed by real time-qPCR for miR-125, miR-374, and miR-669k. [score:1]
Figure 4 The panels report the amplification curves for each one of the 20 mouse lung fragments tested, either adenoma-free (green) or adenoma-bearing (purple), relatively to miRNAs miR-125, miR-374, and miR-669k. [score:1]
[1 to 20 of 7 sentences]
76
[+] score: 14
Other miRNAs from this paper: hsa-mir-205, hsa-mir-125b-1, hsa-mir-125b-2
Further characterization revealed that entinostat upregulated three erbB2/ erbB3 -targeting miRNAs (miR-125a, miR-125b, and miR-205) which acted in concert to inhibit erbB2/erbB3 translation [97]. [score:8]
Our recent data show that entinostat, a class I HDAC inhibitor selectively downregulates erbB2/erbB3 via induction of specific miRNAs, miR-125a, miR-125b, and miR-205 in erbB2+ breast cancer cells. [score:6]
[1 to 20 of 2 sentences]
77
[+] score: 13
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-96, hsa-mir-99a, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-139, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-210, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-134, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-190a, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-370, hsa-mir-373, hsa-mir-374a, hsa-mir-375, hsa-mir-376a-1, hsa-mir-151a, hsa-mir-148b, hsa-mir-331, hsa-mir-338, hsa-mir-335, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-429, hsa-mir-491, hsa-mir-146b, hsa-mir-193b, hsa-mir-181d, hsa-mir-517a, hsa-mir-500a, hsa-mir-376a-2, hsa-mir-92b, hsa-mir-33b, hsa-mir-637, hsa-mir-151b, hsa-mir-298, hsa-mir-190b, hsa-mir-374b, hsa-mir-500b, hsa-mir-374c, hsa-mir-219b, hsa-mir-203b
Izzotti et al. (2009a, b) have monitored the expression of 484 miRNAs in the lungs of mice exposed to cigarette smoking, the most remarkably downregulated miRNAs belonged to several miRNA families, such as let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR-122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223. [score:6]
Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF. [score:6]
Supress cell proliferationGramantieri et al., 2007, 2008; Budhu et al., 2008; Huang et al., 2009; Furuta et al., 2010; Lang and Ling, 2012; Zheng et al., 2012a miR-125a/b/b-2 Inversely correlated with aggressiveness and poor prognosis. [score:1]
[1 to 20 of 3 sentences]
78
[+] score: 13
The study indicated that miR-125a inhibited the proliferation and metastasis of HCC by targeting matrix metalloproteinase II (MMP II) and vascular endothelial growth factor A (VEGF-A) in vivo and in vitro. [score:5]
Therefore, miR-125a up-regulation may be a promising therapeutic agent in HCC. [score:4]
The observed decrease in miR-125a expression in both HCC tissues and cell lines was associated with aggressive pathological features. [score:3]
The role of miR-125a in hepatocellular carcinoma was studied by Bi et al. [60]. [score:1]
[1 to 20 of 4 sentences]
79
[+] score: 12
Increased in Bissels et al. and this studyIncreased in Liao et al. and this studyIncreased in Cattaneo et al. and this study Commonly increased in three studies miR-484 miR-16 nil miR-142-3p miR-425-5p miR-27a miR-142-5p miR-191 Decreased in Bissels et al. and this study Decreased in Liao et al. and this study Decreased in Cattaneo et al. and this study Decreased in Bissels et al. and Cattaneo et al. miR-146a miR-127 miR-126-5p miR-29b-3p miR-146b-5p miR-100 miR-99a miR-10a miR-125b miR-125a-5p These data together suggest a signature of miRNA expression associated with differentiation status and maturation within the myeloid lineage. [score:3]
Increased in Bissels et al. and this studyIncreased in Liao et al. and this studyIncreased in Cattaneo et al. and this study Commonly increased in three studies miR-484 miR-16 nil miR-142-3p miR-425-5p miR-27a miR-142-5p miR-191 Decreased in Bissels et al. and this study Decreased in Liao et al. and this study Decreased in Cattaneo et al. and this study Decreased in Bissels et al. and Cattaneo et al. miR-146a miR-127 miR-126-5p miR-29b-3p miR-146b-5p miR-100 miR-99a miR-10a miR-125b miR-125a-5p These data together suggest a signature of miRNA expression associated with differentiation status and maturation within the myeloid lineage. [score:3]
The important roles of miR-125b and miR-125a in human myelopoiesis is highlighted by their frequent dysregulation in various myeloid malignancies (reviewed in ref. [score:2]
In mouse, levels of miR-125b (and miR-125a) decrease with increasing granulocyte maturity [59]. [score:1]
Interestingly, four of the reduced miRNAs, miR-99a, miR-100, miR-125b, miR-125a-5p, are members of homologous tricistronic clusters involved in stem and progenitor cell homeostasis [37]. [score:1]
For instance, of the miRNAs that decrease with hematopoietic differentiation in our analysis, mouse studies have shown that a decrease in miR-146a is crucial for megakaryocytopoiesis [43] and a decrease in the miR-99a/miR-125a cluster is important for loss of stemness as the cells mature [44]. [score:1]
Several studies in the mouse have identified miR-125b and family member miR-125a as important for various aspects of primitive and leukaemic hemopoiesis [54]. [score:1]
[1 to 20 of 7 sentences]
80
[+] score: 12
The concurrent down-regulation of the miR-let7 cluster, known to promote differentiation in most cells and de-differentiation when it is inhibited [76], miR-125, a highly abundant miRNA in adult retina [45], and miR-7, known to promote photoreceptor differentiation [44] is consistent with Müller cell de-differentiation under the influence of ESMVs. [score:6]
miR-7, which represses the expression of Yan protein and promotes photoreceptor differentiation [44], as well as miR-125-2b, highly abundant in adult retina [45], were down-regulated over 48 hours post-ESMV treatment. [score:6]
[1 to 20 of 2 sentences]
81
[+] score: 12
5 miRNAs (miR-125, miR-126, miR-21, miR-29b and miR-30b) showed a trend of downregulation in the ACVIM C group. [score:4]
The next four analyzed miRNAs–miR-21, miR-29b, miR-125, miR-126 showed a trend of downregulation in the mild to moderate heart failure group–ACVIM B but the results did not reach statistical significance. [score:4]
1: The expression of miR-21, miR-29, miR-30b, miR-133b, miR-126, miR-423 and miR-125 in dogs with heart failure divided into groups based on age (fold changes relative to youngest group; mean ± SEM). [score:3]
The mean fold change for each of them was as follows: -1.84 for miR-30b, -1.55 for miR-126, -1.82 for miR-125. [score:1]
[1 to 20 of 4 sentences]
82
[+] score: 12
MiR-125a-5p was reported to inhibit migration and invasion of lung cancer cells by regulating the expression of several downstream genes of EGFR signaling [74]. [score:5]
Down-regulation of miR-125a-3p and miR-125a-5p in NSCLC could predict a more aggressive clinical course by promoting tumor invasion and lymph node metastasis [76]. [score:4]
Furthermore, miRNA profiling has linked miR-125a-5p expression to metastatic tumor features and lung cancer patient outcome, thus having a potential diagnostic and prognostic impact [75]. [score:3]
[1 to 20 of 3 sentences]
83
[+] score: 12
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-96, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, hsa-mir-16-2, hsa-mir-196a-1, hsa-mir-198, hsa-mir-129-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-196a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-204, hsa-mir-210, hsa-mir-211, hsa-mir-212, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-216a, hsa-mir-217, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-23b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-140, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-129-2, hsa-mir-138-1, hsa-mir-146a, hsa-mir-150, hsa-mir-184, hsa-mir-185, hsa-mir-195, hsa-mir-206, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-365a, hsa-mir-365b, hsa-mir-375, hsa-mir-376a-1, hsa-mir-378a, hsa-mir-382, hsa-mir-383, hsa-mir-151a, hsa-mir-148b, hsa-mir-338, hsa-mir-133b, hsa-mir-325, hsa-mir-196b, hsa-mir-424, hsa-mir-20b, hsa-mir-429, hsa-mir-451a, hsa-mir-409, hsa-mir-412, hsa-mir-376b, hsa-mir-483, hsa-mir-146b, hsa-mir-202, hsa-mir-181d, hsa-mir-499a, hsa-mir-376a-2, hsa-mir-92b, hsa-mir-33b, hsa-mir-151b, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-301b, hsa-mir-216b, hsa-mir-103b-1, hsa-mir-103b-2, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-378b, hsa-mir-320e, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-219b, hsa-mir-203b, hsa-mir-451b, hsa-mir-499b, hsa-mir-378j
Xia et al. (2011) Heart miR-218a-1/2 Zebrafish Knockdown, overexpression, ISH, luciferase reporter assay, qRT-PCR Heart field migration Fish et al. (2011) miR-138 Zebrafish Knockdown, antagomiR, ISH, luciferase reporter assay, qRT-PCR Cardiac patterning Morton et al. (2008) miR-21, miR-218a Zebrafish Knockdown, overexpression, ISH, qRT-PCR, luciferase reporter assay Heart valve formation Chiavacci et al. (2012) and Banjo et al. (2013) let-7e,f,g,h,i,j,k,l,m,n,o, miR-1a, miR-20, miR-21a,b,c, miR-29a,b, miR-103, miR-125, miR-126a,b, miR-128c, miR-145, and miR-199b Asian seabass qRT–PCR ? [score:5]
In Sertoli cell-specific Dicer conditional knockout mouse mo del, miR-125a-3p, miR-872, and miR-24 have role in translational control during spermatogenesis (Papaioannou et al. 2011). [score:4]
Ma et al. (2012) let-7g, k, h, i, l, miR-29a, b, miR-103, miR-124a, b, c, d, and miR-125 Asian seabass qRT–PCR ? [score:1]
Soares et al. (2009) let-7a,b,c,f,i, miR-7b, miR-9-5p, miR-9-3p, miR-34b, miR-103, miR-107, miR-124a, miR-125a,b, miR-128, miR-129-3p, miR-132, miR-138, miR-181a,b, miR-216, miR-217, miR-219, and miR-375 Zebrafish Microarray, ISH ? [score:1]
Wienholds et al. (2005) let-7g,n,k,h,i,l, miR-21c, miR-29a,b, miR-124, miR-125, miR-126a,b, miR-181a,b, miR-183a,b, miR-184a,b Asian seabass qRT–PCR ? [score:1]
[1 to 20 of 5 sentences]
84
[+] score: 12
Other miRNAs from this paper: hsa-mir-125b-1, hsa-mir-125b-2
The miRNA-125 family (miRNA-125a-3p, miRNA-125a-5p, miRNA-125b-1, and miRNA-125b-2) is highly-conserved in many species, and expression of these miRNAs regulates carcinogenesis and tumor development by targeting many tumor-promoting and -suppressing transcription factors [27, 28]. [score:9]
In miR125 -expressing Huh6 cells, cell cycle progression at the G0/G1 phase decreased approximately 2-fold (Figure 3C). [score:3]
[1 to 20 of 2 sentences]
85
[+] score: 12
Calin et al. reported that one of the most upregulated miRNAs is miR-106a, which is consistently reported in six studies, and the five most downregulated miRNAs are miR-30a-3p, miR-139, miR-145, miR-125a, and miR-133a, which are consistently reported and differentially expressed in four studies; these miRNAs may actually be of clinical use as diagnostic/prognostic biomarkers or therapeutic targets [3]. [score:11]
On the other hand, we found seven statistically significant miRNAs, namely, miR-145, miR-363, miR-378*, miR-137, miR-100, miR-125a-5p, miR-143 in conditional forward method. [score:1]
[1 to 20 of 2 sentences]
86
[+] score: 11
Developmental stage of O. felineus miRNAs AdultNoEggs & Adult+Eggs & Metacercaria let-7, miR-1, miR-2(a,b,c,d,e), miR-36, miR-71(a,b), miR-124, miR-125, miR-133, miR-190 AdultNoEggs & Adult+Eggs bantam, miR-281(miR-46 family) AdultNoEggs & Metacercaria miR-7 Metacercaria miR-10 Candidate sequences for novel miRNAs (S4 Table) were selected from reads without matches to miRBase sequences after mapping them to the C. sinensis genome and processing the genomic fragments encompassing the resultant hits through the secondary structure filter (see ). [score:2]
Developmental stage of O. felineus miRNAs AdultNoEggs & Adult+Eggs & Metacercaria let-7, miR-1, miR-2(a,b,c,d,e), miR-36, miR-71(a,b), miR-124, miR-125, miR-133, miR-190 AdultNoEggs & Adult+Eggs bantam, miR-281(miR-46 family) AdultNoEggs & Metacercaria miR-7 Metacercaria miR-10Candidate sequences for novel miRNAs (S4 Table) were selected from reads without matches to miRBase sequences after mapping them to the C. sinensis genome and processing the genomic fragments encompassing the resultant hits through the secondary structure filter (see ). [score:2]
The next miRNA cluster that should be discussed is let-7/miR-100/miR-125. [score:1]
This could be due to the incompleteness of either genome assembly (miR-125 was not found in C. sinensis genome) or indeed by the species specificity of miRNA genes (we did not find the opisthorchid miR-1 in S. japonicum genome, we also did not locate opisthorchid miR-36b in either schistosome genome). [score:1]
Second, the combination of let-7/ miR-125 genes is unlikely to exist as a synteny group, as the two miRNA genes map to different chromosomes in S. mansoni (S9 Table). [score:1]
S9 TableLocation of lin-7 and miR-125 in flatworms genomes according miRBase (Release 21: June 2014 http://mirbase. [score:1]
The ortholog search for the miRNAs of the three opisthorchiids yielded 19 conserved miRNAs belonging to 13 families (bantam, let-7, miR-1, miR-2, mir-7, miR-10, miR-36, miR-46, miR-71, miR-124, miR-125, miR-133, and miR-190) (Fig 2A, Table 1, S3 Table). [score:1]
Location of lin-7 and miR-125 in flatworms genomes according miRBase (Release 21: June 2014 http://mirbase. [score:1]
miRNA Genomes C. sinensis S. mansoni S. japonicum bantam + + + let-7 + + + miR-1 + + − miR-2a + + + miR-2b + + + miR-2c + + + miR-2d + + + miR-2e + + + miR-7 + + + miR-10 + + + miR-36a + + + miR-36b + − − miR-281 + + + miR-71a + + + miR-71b + + + miR-124 + + + miR-125 − + + miR-133 + + + miR-190 + + + Mapped miRNA is designated by plus; unmapped—by minus. [score:1]
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87
[+] score: 11
Eight miRNAs, namely miR-125a-5p, -125b-5p, -126-3p, -210-3p, -494-3p, -21-5p, -29a-3p and -320a were significantly up-regulated in HF (vs. [score:4]
The up-regulation of these miRNAs in HF is supported by studies demonstrating that serum miR-125a-5p is significantly increased in human HF [3], and is one of the most abundant miRNA in pericardial fluid from HF patients undergoing open-heart surgery [37]. [score:4]
Validation of a selected few by qPCR identified 10 miRNAs - miR-133b-3p, miR-208b-3p, miR-21-5p, miR-125a-5p, miR-125b-5p, miR-126-3p, miR-210-3p, miR-29a-3p, miR-494-3p and miR-320a, that were significantly up-regulated in HF myocardium compared to normal controls. [score:3]
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88
[+] score: 11
The other five miRNAs common on the three mo dels (miR-21a-5p, miR-125a-5p, miR-142a-3p, miR-146b-5p, and miR-342-3p) also have important immunological activities (Table 1) that would together favor antibody production and development of the murine disease. [score:4]
Six of them were down- (miR-142a-3p, miR-146b-5p, and miR-155-5p) or upregulated (miR-21a-5p, miR-125a-5p, and miR-200a-3p) in the three lupus-like murine mo dels while the other six were affected in two or only one of them (Figure 2(b)). [score:4]
The PCR amplification was run as described by the TaqMan Universal PCR Master Mix manual (Applied Biosystems) for the following differentially expressed miRNAs, as determined by PCR array analysis: miR-21a-5p, miR-125a-5p, miR-142-3p/5p, miR-146b/5p, miR-155-5p, and miR-200a-3p. [score:3]
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89
[+] score: 11
Similarly to our recent observation (Funikov et al., 2016), the expression levels of several clustered miRNAs respond to HS individually and independently of each other: in the cluster let-7, mir-100, mir-125 HS up-regulates let-7 expression, but down-regulates mir-100. [score:11]
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90
[+] score: 11
Of the miRNAs selected for comparison, two miRNAs (dre-miR-31 and dre-miR-430a) were up-regulated whereas two miRNAs (dre-miR-125a and dre-miR-126) were down-regulated based on the results of microarray analysis. [score:7]
In the present studies, expression changes in miR-430 and miR-125 families were quite significant. [score:3]
To validate the microarray data, we assayed expression levels of four miRNAs (dre-miR-125a, dre-miR-126, dre-miR-31, and dre-miR-430a) by qPCR and compared the results from the microarray and qPCR. [score:1]
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91
[+] score: 11
Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. [score:5]
However, miR-125-5p expression showed no change in human AD samples and exhibited a slight decrease in the mouse AD mo del (data not shown) and hence, may not be relevant to the pathogenesis of AD. [score:3]
PSD-95 was identified as a target of miR-125-5p (Muddashetty et al., 2011). [score:3]
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92
[+] score: 11
For instance, Raponi and colleagues have identified 15 differentially expressed miRNAs between SCCs and healthy lung tissues, among which let-7e and miR-125a were downregulated while the remaining 13 miRNAs were upregulated (Raponi et al., 2009). [score:9]
85 HCs 221 NSCLCs, 161 HCs, 56 with benign nodules Serum Plasma RT-qPCR RT-qPCR TaqMan Low Density Array, RT-qPCR U6 U6 let-7d/g/i trioChen et al., 2015; Li et al., 2015; Powrózek et al., 2015 miR-125a-5p, miR-145 miR-146a (up) 70 NSCLCs vs. [score:1]
Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer. [score:1]
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93
[+] score: 11
In four FET placenta-specific miRNAs, there was no significant correlation between miRNA expression and maternal age, whereas there were weak correlations between expression levels of miR-125a-5p, miR-224-3p, miR-331-3p, miR-365a-3p, miR-518b, miR-518f-3p, and miR-543 and maternal age (Additional file 7: Table S5). [score:5]
The boxplots show the expression levels of miR-197-5p (a), miR-4697-5p (b), miR-4721 (c), miR-5006-5p (d), miR-575 (e), miR-6893-5p (f), miR-125a-5p (g), miR-1260b (h), miR-224-3p (i), miR-331-3p (j), miR-365a-3p (k), miR-495-3p (l), miR-518b (m), miR-518f-3p (n), miR-543 (o) and miR-7977 (p). [score:3]
Nine (miR-125a-5p, miR-224-3p, miR-331-3p, miR-365a-3p, miR-495-3p, miR-518b, miR-518f-3p, miR-543, and miR-7977) were significantly downregulated in FET placentae compared with SP, but not ET (Fig. 2 and Additional file 5: Figure S1). [score:3]
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94
[+] score: 11
Other miRNAs from this paper: hsa-mir-17, hsa-mir-22, hsa-mir-125b-1, hsa-mir-125b-2
Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro -RNA miR-125a or miR-125b. [score:5]
Concurrently, the overexpression of miR-125a/b was found to reduce ErbB2/3 at both the transcript and protein level in the human breast cancer cell line SKBR3 thereby reducing AKT signaling [30]. [score:3]
In support of our findings, a similar LCM study found miR-125 to be down-regulated 2.2-fold in pooled FFPE prostate cancer samples compared to their normal counterparts (5 Caucasians and 5 African) [35]. [score:3]
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95
[+] score: 11
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-96, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-16-2, hsa-mir-197, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-199a-2, hsa-mir-204, hsa-mir-210, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-140, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-138-1, hsa-mir-146a, hsa-mir-193a, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-194-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34b, hsa-mir-34c, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-363, hsa-mir-365a, hsa-mir-365b, hsa-mir-369, hsa-mir-370, hsa-mir-371a, hsa-mir-375, hsa-mir-378a, hsa-mir-133b, hsa-mir-423, hsa-mir-448, hsa-mir-429, hsa-mir-486-1, hsa-mir-146b, hsa-mir-181d, hsa-mir-520c, hsa-mir-499a, hsa-mir-509-1, hsa-mir-532, hsa-mir-33b, hsa-mir-637, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-509-2, hsa-mir-208b, hsa-mir-509-3, hsa-mir-103b-1, hsa-mir-103b-2, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-378b, hsa-mir-320e, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-371b, hsa-mir-499b, hsa-mir-378j, hsa-mir-486-2
[192] miR-33b Decrease lipogenesis via early B cell factor 1 (EBF1) targeting C/EBPα and PPARγ signaling[193] miR-93 Sirt7 and Tbx3[194] miR-125a ERRα[195] miR-130 Inhibition of adipogenesis by inhibiting PPARγ[66] miR-138 Inhibition of adipocyte differentiation via EID-1. Lipid droplet reduction[196] miR-145 Preadipocyte differentiation by targeting IRS1[197] miR-155 C/EBPβ pathway[198] mirR-193a/b Adiponectin production in the adipose tissue. [score:11]
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96
[+] score: 11
A luciferase reporter assay has been used to confirm that circPVT1 acts as a sponge of the tumor suppressor miR-125 family, and also indirectly regulates the expression of the transcription factor, E2F2, which plays a crucial role in the control of the cell cycle and action of tumor suppressor proteins [66]. [score:8]
Therefore, circPVT1 has the potential to promote colony formation of gastric cancer cells via inhibition of miR-125 [66]. [score:3]
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97
[+] score: 10
After determining the expression levels of these miRNAs in the same 7 pairs of NSCLC tissues and normal adjacent tissues, we observed that 8 miRNAs (miR-203, miR-30, let-7, miR-132, miR-181, miR-212, miR-101 and miR-9) were downregulated in the NSCLC tissues, while the other 5 miRNAs (miR-125, miR-98, miR-196, miR-23 and miR-499) were upregulated (Fig. S1). [score:9]
A total of 13 miRNAs, including miR-203, miR-30, let-7, miR-132, miR-181, miR-212, miR-101, miR-9, miR-125, miR-98, miR-196, miR-23 and miR-499, were identified as candidate miRNAs by all three computational algorithms (Table S2). [score:1]
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98
[+] score: 10
We also verified the previously reported down-regulation of miR-30a-3p [22], miR-10b, miR-30c, miR-125a, miR-1, miR-133a, and miR-195 [35]. [score:4]
miRNA fold change location CRC Fragile site* hsa-miR-20a up 13q31.3 gain hsa-miR-19a up 13q31.3 gain hsa-miR-17-5p up 13q31.3 gain hsa-miR-93 up 7q22.1 gain hsa-miR-25 up 7q22.1 gain hsa-miR-31 up 9p21.3 hsa-miR-106a up Xq26.2 hsa-miR-143 down 5q32 loss hsa-miR-145 down 5q32 loss hsa-miR-125a down 19q13.41 gain hsa-miR-1 down 18q12.3 or 20q13.33 loss (18q) or gain (20q)* Summarized from [41- 43] Figure 4 Expression of 14 miRNAs in 8 CRC cell lines and normal colon total RNA. [score:3]
miRNA fold change location CRC Fragile site* hsa-miR-20a up 13q31.3 gain hsa-miR-19a up 13q31.3 gain hsa-miR-17-5p up 13q31.3 gain hsa-miR-93 up 7q22.1 gain hsa-miR-25 up 7q22.1 gain hsa-miR-31 up 9p21.3 hsa-miR-106a up Xq26.2 hsa-miR-143 down 5q32 loss hsa-miR-145 down 5q32 loss hsa-miR-125a down 19q13.41 gain hsa-miR-1 down 18q12.3 or 20q13.33 loss (18q) or gain (20q)* Summarized from [41- 43] Figure 4 Expression of 14 miRNAs in 8 CRC cell lines and normal colon total RNA. [score:3]
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99
[+] score: 10
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-20a, hsa-mir-21, hsa-mir-28, hsa-mir-29a, hsa-mir-93, hsa-mir-100, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-107, hsa-mir-16-2, hsa-mir-196a-1, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-34a, hsa-mir-181c, hsa-mir-182, hsa-mir-196a-2, hsa-mir-199a-2, hsa-mir-210, hsa-mir-217, hsa-mir-223, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-27b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-141, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-134, hsa-mir-138-1, hsa-mir-146a, hsa-mir-150, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-106b, hsa-mir-29c, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-372, hsa-mir-382, hsa-mir-148b, hsa-mir-196b, hsa-mir-424, hsa-mir-448, hsa-mir-449a, hsa-mir-483, hsa-mir-491, hsa-mir-501, hsa-mir-503, hsa-mir-548a-1, hsa-mir-548b, hsa-mir-548a-2, hsa-mir-548a-3, hsa-mir-548c, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-320c-1, hsa-mir-548e, hsa-mir-548j, hsa-mir-548k, hsa-mir-548l, hsa-mir-548f-1, hsa-mir-548f-2, hsa-mir-548f-3, hsa-mir-548f-4, hsa-mir-548f-5, hsa-mir-548g, hsa-mir-548n, hsa-mir-548m, hsa-mir-548o, hsa-mir-548h-1, hsa-mir-548h-2, hsa-mir-548h-3, hsa-mir-548h-4, hsa-mir-548p, hsa-mir-548i-1, hsa-mir-548i-2, hsa-mir-548i-3, hsa-mir-548i-4, hsa-mir-320c-2, hsa-mir-548q, hsa-mir-548s, hsa-mir-548t, hsa-mir-548u, hsa-mir-548v, hsa-mir-548w, hsa-mir-548x, hsa-mir-548y, hsa-mir-548z, hsa-mir-548aa-1, hsa-mir-548aa-2, hsa-mir-548o-2, hsa-mir-548h-5, hsa-mir-548ab, hsa-mir-548ac, hsa-mir-548ad, hsa-mir-548ae-1, hsa-mir-548ae-2, hsa-mir-548ag-1, hsa-mir-548ag-2, hsa-mir-548ah, hsa-mir-548ai, hsa-mir-548aj-1, hsa-mir-548aj-2, hsa-mir-548x-2, hsa-mir-548ak, hsa-mir-548al, hsa-mir-548am, hsa-mir-548an, hsa-mir-548ao, hsa-mir-548ap, hsa-mir-548aq, hsa-mir-548ar, hsa-mir-548as, hsa-mir-548at, hsa-mir-548au, hsa-mir-548av, hsa-mir-548aw, hsa-mir-548ax, hsa-mir-548ay, hsa-mir-548az, hsa-mir-548ba, hsa-mir-548bb, hsa-mir-548bc
Among them, miR-199a-3p targets HBsAg coding region and the pre-S region of the HBV genome, whereas miR-125a-5p binds to HBsAg mRNA leading to inhibition of its translation [46, 68]. [score:7]
The miRNAs shown to reduce HBV replication and the expression of HBV surface antigen (HBsAg) are miR-199a-3p, miR-210 and miR-125a-5p. [score:3]
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100
[+] score: 10
Accordingly, we found that 4 of the miRNAs with the highest enrichment after infection (miR-125a, miR146b, miR-3661, and miR-151b) are all up-regulated following infection, and strongly so after 24h of infection (Fig 6B). [score:4]
Specifically, our data support previous hypotheses and find evidence for that 3’ UTR shortening in macrophages is associated with the loss of target sites for a subset of immune-regulated miRNAs, including miR-146b, miR-125a, and miR-151b (Fig 6B). [score:4]
Interestingly, of the miRNAs with the highest enrichment after infection with either Listeria or Salmonella, two (miR-146b and miR-125a) have previously been shown to be important regulators of the innate immune response [47– 51]. [score:2]
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