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20 publications mentioning mmu-mir-361

Open access articles that are associated with the species Mus musculus and mention the gene name mir-361. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

[+] score: 426
miR-101 downregulation leads to overexpression of its negative feedback regulator, EZH2, which acts as a co-suppressor of YY1 to epigenetically suppress miR-361, upregulating Twist (a direct target of miR-361). [score:17]
Similar to miR-361 overexpression, Twist knockdown in SPAC-1-L cells downregulated pro-angiogenic and immunosuppressive cytokines (IL-6 and IL-8), and upregulated IFN-α and IFN-γ, which are known to stimulate antitumor immunity and process anti-angiogenic effects [15] (Figure 2G and Supplementary Figure 5). [score:12]
Figure 1(A) miRNA profiling showing miRNAs (103 upregulated and 72 downregulated) differentially expressed in miR-101 mimic -transfected SPAC-1-L cells compared with controls Venn diagram depicts overlapping miRNAs (let-7b, miR-361 and miR-378) that may be EZH2-regulated tumor suppressors. [score:11]
We further demonstrated that EZH2 upregulates expression of Twist, a direct target of miR-361, via direct repression of miR-361 through a YY1 -dependent mechanism. [score:10]
EZH2 silencing in SPAC-1-L cells upregulated E-cadherin and downregulated mesenchymal/stem cell markers and MMSET (a target of EZH2), similar to the effects of miR-361 mimics. [score:9]
EZH2 inhibition by the specific inhibitor GSK343 is sufficient to induce miR-361 expression, decrease Twist levels and inhibit EC cell proliferation and invasiveness in vitro. [score:9]
Ectopic expression of the miR-361 precursor reduced Twist mRNA and protein levels in SPAC-1-L cells, while miR-361 inhibition upregulated Twist in Ishikawa cells (Figure 2B and Supplementary Figure 3C). [score:8]
let-7b and miR-361 overexpression in SPAC-1-L and HOUA-I cells enhanced E-cadherin expression and downregulated Vimentin and phospho-AKT (Figure 1O). [score:8]
Together, these data suggested that miR-361 overexpression impairs EMT in EC cells by directly targeting Twist and indirectly up -regulating epithelial markers, such as E-cadherin. [score:8]
In contrast, ectopic Twist expression mimicked the effects of miR-361 inhibition on downstream gene expression in Ishikawa cells (Figure 2F, and Supplementary Figure 4A and 4F). [score:7]
As single agents, GSK343 and 5-AZA suppress EC cell proliferation, migration and invasion, but their combination synergistically upregulated miR-361 and enhanced inhibition of cell growth, migration and invasion as compared to either agent alone (Figure 4F). [score:7]
This upregulates Twist, a direct target of miR-361 in EC cells (Figure 5C). [score:7]
We report that EZH2 directly downregulates miR-361, a novel Twist suppressor, in EC cells. [score:7]
Twist overexpression in Ishikawa cells phenocopied the effects of anti-miR-361 inhibitor treatment and induced IL-6 and IL-8 expression, but reduced INF-α and IFN-γ (Figure 2H and Supplementary Figure 5). [score:7]
In the presence of let-7b or miR-361, epithelial marker (E-cadherin, ZO-1 and DSP) mRNAs were upregulated, whereas mesenchymal, stemness, and drug resistance markers (Snail, N-cadherin, BMI1, S100A4, OCT4 and MDR1) were downregulated in SPAC-1-L cells (Figure 1P and Supplementary Figure 2C). [score:7]
In contrast, in aggressive SPAC-1-L cells expressing the lowest let-7b and miR-361 levels, transient overexpression of either miRNA using mimics suppressed in vitro cell invasion and proliferation (Figure 1K–1L and Supplementary Figure 2A, right panel). [score:7]
We found that EZH2 inhibition by GSK343 effectively restored miR-361 expression and phenocopied the effects of EZH2 knockdown in vitro. [score:6]
Reporter constructs containing either wild-type (W) Twist 3′-UTR, or with mutation (M) at the predicted miR-361 target sequence were co -transfected into SPAC-1-L (C) or Ishikawa (D) cells, along with miR-361 mimic, anti-miR-361 inhibitor, or negative control. [score:6]
To test whether EZH2 directly represses miR-361 transcription, we cloned the three binding sites (2, 5 and 8) into a pGL3 luciferase vector (Figure 3H) and used site-directed mutagenesis to generate mutations targeting YY1 binding sites. [score:6]
EZH2 inhibition reduced self-renewal and Twist expression, which was partially reversed by miR-361 knockdown (Supplementary Figure 8A and 8C). [score:6]
We identified tumor-suppressive let-7b and miR-361 as EZH2 -downregulated miRNAs that attenuate EC cell proliferation, invasiveness, and cancer stem cell-like properties. [score:6]
We demonstrated that miR-361 is a tumor suppressor in EC, and EZH2 binds directly to the miR-361 promoter to suppress its transcription through a YY1 -dependent manner. [score:6]
Here, we examined whether Twist downregulation is responsible for miR-361 -mediated tumor suppression in aggressive, serous EC SPAC-1-L cells. [score:6]
Reactivating miR-361 by targeting its upstream regulator, EZH2, may have promising therapeutic potential against EZH2-active or -overexpressing tumors. [score:6]
Our in vivo results corroborated our in vitro data and support the notion that epigenetic silencing of miR-361 by EZH2 upregulates Twist expression in EC. [score:6]
qRT-PCR results demonstrated miR-361 upregulation after siRNA -mediated YY1 knockdown (Figure 3E), suggesting that YY1 might regulate miR-361 in EC cells. [score:6]
Our microarray and qRT-PCR analyses demonstrated that the miR-101 mimic, a direct regulator of EZH2 [6], upregulated let-7b and miR-361 (Figures 1A and 3A). [score:6]
EZH2 overexpression resulting from miR-101 loss could indirectly activate important oncogenes via suppression of let-7b or miR-361. [score:6]
showed that YY1 expression decreased upon EZH2 knockdown in SPAC-1-L cells, and increased following transient EZH2 overexpression in Ishikawa cells (Figure 3B), suggesting that EZH2 induces and functions together with its recruiter, YY1, to silence miR-361. [score:6]
Given that EZH2 epigenetically suppresses multiple tumor suppressor miRNAs [7], we assessed whether EZH2 silenced let-7b and miR-361 in EC cells. [score:5]
Both let-7b and miR-361 were upregulated following EZH2 knockdown (Figure 3A–3B and Supplementary Figure 6A). [score:5]
Moreover, EZH2 overexpression promoted Ishikawa cell invasion and increased Twist expression; however, miR-361 induction abrogated these effects (Supplementary Figure 8B and 8D). [score:5]
siRNA -mediated Twist knockdown reduced cell invasion, migration, and sphere formation similarly to miR-361 overexpression, with consequent effects on Twist-regulated downstream genes (Figure 2E and Supplementary Figure 4A–4E). [score:5]
Given that let-7b is a known tumor suppressor [9], we focused on miR-361 to determine its molecular targets. [score:5]
However, mutated-type promoter luciferase activity was not affected by EZH2 overexpression or YY1 inhibition (Figure 3H and Supplementary Figure 7A), suggesting that EZH2 silences miR-361 transcription in a YY1 -dependent fashion. [score:5]
This supports the idea that let-7b and miR-361 function as tumor suppressors, maintaining the epithelial phenotype and inhibiting PI3K/AKT signaling in EC. [score:5]
To establish the clinical significance of altered miR-361 expression in EC progression, we examined the association between miR-361 expression and clinicopathologic variables. [score:5]
In agreement with previous studies showing that numerous miRNAs are silenced by EZH2 in human cancer cells [7, 16], in EC cells, EZH2 mediated suppression of let-7b and miR-361, both of which inhibit EC cell proliferation, invasion and self-renewal. [score:5]
We divided 24 EC patients into two groups: those with lower than average miR-361 expression (n = 12) and those with higher than average miR-361 expression (n = 12). [score:5]
Subsequent meta-analysis using TCGA database showed that increased expression of EZH2 or Twist was associated with poorer prognosis in EC patients (Figure 5B), suggesting an inverse correlation between EZH2/Twist and miR-361 expression in EC. [score:5]
200 targets shared by all algorithms included the reported miR-361 target, VEGFA [10] (Supplementary Figure 3A). [score:5]
To investigate whether Twist is a direct target of miR-361, a luciferase reporter vector containing the Twist 3′-untranslated region (UTR) and miR-361 mimic were co -transfected into SPAC-1-L cells. [score:4]
To elucidate their biological functions, we transiently knocked them down with anti-miRNA inhibitors in less-aggressive Ishikawa cells, which have high endogenous let-7b and miR-361 levels (Supplementary Figure 2A, left panel). [score:4]
We then examined whether EZH2 regulates miR-361 downstream targets. [score:4]
Twist, a novel oncogene that promotes EC cell EMT and invasion [2], was predicted to be a direct miR-361 target (Figure 2A and Supplementary Figure 3A). [score:4]
GSK343 treatment mimics EZH2 knockdown effects on miR-361 and Twist expression. [score:4]
Together, our results identify a pathway, EZH2-miR-361-Twist, that positive regulates tumor malignancy by promoting cancer cell proliferation, invasion, and self-renewal, and further support EZH2 as a promising therapeutic anti-EC target. [score:4]
let-7b or miR-361 downregulation led to a more scattered and mesenchymal morphology, a hallmark of the EMT process (Figure 1J), and promoted Ishikawa cell invasion and proliferation (Figure 1K–1L). [score:4]
EZH2 and Twist levels were increased in EC samples (Figure 5A), while miR-361 was downregulated (Figure 1C). [score:4]
GSK343 mimics the effects of EZH2 knockdown on miR-361 and Twist expression. [score:4]
miR-361 directly targets Twist and modulates downstream genes. [score:4]
A sphere formation assay revealed that let-7b or miR-361 overexpression suppressed SPAC-1-L sphere formation and sensitized cells to paclitaxel. [score:4]
let-7b and miR-361 are tumor suppressors potentially regulated by EZH2. [score:4]
Similar to EZH2 knockdown, GSK343 treatment enhanced miR-361 and E-cadherin levels, and decreased the expression of Snail, N-cadherin, Twist and Vimentin (Figure 4A, 4F and Supplementary Figure 8F). [score:4]
VEGFA inhibition by miR-361 was validated in two of three EC cell lines examined (Supplementary Figure 3B). [score:3]
We then surveyed miR-361 and EMT-related marker expression. [score:3]
We also observed increased sphere-forming capacity and reduced sensitivity to paclitaxel in let-7b or miR-361 -inhibited Ishikawa cells (Figure 1M–1N and Supplementary Figure 2B). [score:3]
Either wild type or mutant miR-361-promoter plasmids were co -transfected into Ishikawa cells along with an EZH2 expression vector and YY1 siRNA. [score:3]
Mutation of the miR-361 seed sequence prevented miR-361 -dependent regulation of luciferase activity (Figure 2D). [score:3]
5-AZA treatment also induced miR-361 expression (Supplementary Figure 10), indicating that miR-361 silencing in EC cells is mediated, at least in part, by DNA methylation. [score:3]
We further tested whether let-7b and miR-361 inhibited cancer stem-like phenotypes and drug resistance. [score:3]
These changes were reversed by anti-let-7b and anti-miR-361 expression in Ishikawa cells (Figure 1P and Supplementary Figure 2C). [score:3]
miR-361 suppressed Twist 3′-UTR reporter activity (Figure 2C). [score:3]
Similar analysis of TCGA datasets comprising multiple cancer types also demonstrated reduced let-7b and miR-361 expression in high-risk cancers (Supplementary Figure 1). [score:3]
We also analyzed KEGG pathway enrichment using DIANA-mirPath to explore predicted miR-361 target gene biological pathways. [score:3]
EZH2 -induced invasion and stemness require miR-361 inhibition. [score:3]
miR-361 inhibition in Ishikawa cells increased Twist 3′-UTR luciferase activity. [score:3]
Figure 2(A) Schematic representation of putative miR-361 target site within the human Twist 3′-UTR as predicted by three computational databases. [score:3]
Of these, three (let-7, miR-361 and miR-378) were upregulated by EZH2 knockdown in DU145 prostate cancer cells [7], and were selected as the top candidates for further investigation (Figure 1A). [score:3]
MiR-361 directly targets Twist and modulates its downstream genes. [score:3]
Expression of let-7b (B), miR-361 (C) and miR-378 (D) as assessed by qRT-PCR in 24 EC and adjacent normal tissues. [score:3]
Both let-7b and miR-361 levels were lower in EC than in EM cells (Figure 1I), indicating that these two miRNAs may function as tumor suppressors. [score:3]
Our clinical data combined with TCGA dataset analysis also associated reduced let-7b and miR-361 levels with worse patient survival rates, implicating these miRNAs as potential tumor suppressors across diverse cancer types. [score:3]
A quick-change site-directed mutagenesis kit (Stratagene, CA) was used to mutate the miR-361 binding site within the Twist 3′-UTR or YY1 binding sites on the miR-361 promoter. [score:2]
Using a computational bioinformatics analysis, we screened CpG islands upstream of miR-361, but detected no CpG-enriched region (data not shown), indicating that miR-361 induction by 5-AZA might result from epigenetic activation of an upstream miR-361 regulator. [score:2]
These data demonstrated that miR-361 is a key mediator downstream of EZH2, and that disruption of an EZH2-miR-361-Twist regulatory axis may contribute to EC. [score:2]
To determine whether EZH2 and YY1 associate with the miR-361 promoter in vitro, we performed chromatin immunoprecipitation (ChIP)-qPCR assays with antibodies against EZH2, H3K27me3, and YY1 using lysates from SPAC-1-L cells that express endogenous EZH2 and YY1. [score:2]
YY1 knockdown significantly reduced EZH2 and H3K27me3 recruitment to the miR-361 promoter (site 2, 5 and 8; Figure 3G). [score:2]
To determine whether EZH2 -induced malignancy requires miR-361 silencing, we performed cell invasion and sphere formation assays using SPAC-1-L cells transfected with EZH2 or control siRNA, with or without anti-miR-361 inhibitor. [score:2]
These data indicate that miR-361 mediates aspects of the tumor microenvironment through Twist regulation. [score:2]
To investigate the molecular mechanism by which EZH2 downregulates miR-361, we retrieved the promoter sequence (5000 bp) upstream of miR-361 and searched for all potential transcriptional factor binding sites using the TRANSFAC database. [score:2]
This confirmed the direct repression of Twist by miR-361. [score:2]
The miR-361 seed sequence is evolutionarily conserved between human (H), pig (P), rat (R), mouse (M), and dog (D). [score:1]
Reduced miR-361 was associated with poorly differentiated histology (Supplementary Table 3), indicating that miR-361 repression is important for EC growth and/or progression. [score:1]
To our knowledge, this is the first report linking the EMT process triggered by EZH2-miR-361-Twist signaling to a gene cluster that contains various cytokines (IL-6/8 and IFN-α/γ) and an angiogenic factor (VEGFA). [score:1]
EZH2 binds to and transrepresses the miR-361 promoter via YY1. [score:1]
Clinical relevance of the EZH2–miR-361-Twist axis in EC. [score:1]
GSK343 plus 5-AZA synergistically activated miR-361 and attenuated tumor cell metastatic potential. [score:1]
Lower let-7b (Figure 1E–1F) and miR-361 (Figure 1G–1H), but not miR-378 levels, were associated with worse outcomes (high-risk group). [score:1]
We found 10 binding sites (CCAT) for YY1 (Figure 3D and Supplementary Figure 6B), which recruits the polycomb complex to repress let-7a and miR-29b/c [17, 18], and hypothesized that YY1 may play a role in EZH2 recruitment to the miR-361 promoter. [score:1]
Here, we analyze EZH2 -mediated transcriptional repression in EC cells and describe previously unrecognized functional interactions between EZH2, miR-361, and Twist. [score:1]
These data collectively suggest that miR-361 attenuates EC cell invasion and metastasis through modulation of Twist -dependent and -independent pathways, and potentially reprograms the tumor microenvironment, resulting in tumor regression. [score:1]
Mutating the miR-361 -binding site in the Twist 3′-UTR eliminated luciferase repression by miR-361 (Figure 2C). [score:1]
EZH2, H3K27me3, and YY1 occupied the region of the miR-361 promoter (sites 2, 5 and 8) similar to EZH2/H3K27me3/YY1 binding to the let-7a promoter [17] (Figure 3F). [score:1]
Box plots show lower let-7b (E– F) or miR-361 (G– H) levels in high-risk patients. [score:1]
To construct pri-miR-361 promoter luciferase reporter vectors, the promoter region encompassing YY1 binding sites (2, 5 or 8) was amplified from human genomic DNA and cloned into pGL3 vector MluI/ BglII sites (Promega). [score:1]
We first evaluated let-7b and miR-361 expression in three EC cell lines and the immortalized human endometrial epithelial cell line, EM, using qRT-PCR. [score:1]
Ishikawa cells were transfected with wild type (WT) or mutant (MUT) pri-miR-361 promoter luciferase reporter vector (site 5) along with EZH2 vector, empty vector, Si-YY1, or Si-NC. [score:1]
We then tested the effects of let-7b and miR-361 on EMT markers and PI3K/AKT signaling. [score:1]
Representative images of spheres (scale bar: 100 μm) taken at 14 d. (F) miR-361 expression, proliferation, migration and invasion in SPAC-1-L and HOUA-I cells treated with 5-AZA (10 μM) and/or GSK343 (1 μM) for 72 h. Measurement of Ishikawa-derived xenograft tumors after treatment with GSK343 and 5-AZA alone or in combination. [score:1]
EZH2 epigenetically silences miR-361 via YY1. [score:1]
Although Twist -induced EMT and stemness could account for the malignant phenotypes caused by miR-361 loss, miR-361 may also limit EC progression through other mechanisms. [score:1]
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[+] score: 416
Other miRNAs from this paper: mmu-mir-221
In addition, immunohistochemical staining showed that miR-361-5p expression was significantly lower in the CRC tissues with positive SND1 expression than those with negative SND1 expression, suggesting an inverse relationship between miR-361-5p expression and SND1 expression (Figure 4E). [score:11]
Furthermore, we demonstrated that SND1 inhibited miR-361-5p expression by directly binding to pre-miR-361-5p, subsequently leading to downregulation of mature miR-361-5p expression. [score:11]
The overexpression of miR-361-5p decreased the endogenous expression of SND1 mRNA and protein, whereas anti-miR-361-5p inhibitor increased the expression of SND1 mRNA and protein (Figure 4B). [score:9]
Taken together, these results suggest that the miR-361-5p expression is frequently down-regulated in GC and CRC, and is correlated with poor prognosis, suggesting that miR-361-5p functions as a tumor suppressor in CRC and GC development. [score:9]
Interestingly, we found that upregulation of SND1 decreased the expression of miR-361-5p, while depletion of SND1 increased the expression of miR-361-5p to 2.1-fold higher than the control group. [score:8]
miR-361-5p overexpression inhibited tumor growth and metastasis in CRC and GC cells through the down-regulation of SND1. [score:8]
On the other hand, SND1 overexpression significantly abrogated the inhibitory effect of miR-361-5p on cell proliferation (Figure 5B), suggesting that miR-361-5p exerts tumor-suppressive function in CRC via directly binding to SND1. [score:8]
MiR-361-5p, which is known as a tumor-suppressor miRNA, is down-regulated in human tumors and plays functional roles in several aspects of tumor development and progression [7, 24]. [score:7]
The target prediction programs miRBase and TargetScan were used to predict the possible miR-361-5p targets. [score:7]
miR-361-5p downregulates SND1 expression by directly binding to its 3′-UTR. [score:7]
On the contrary, miR-361-5p overexpression strongly up-regulated the epithelial marker E-cadherin. [score:6]
Figure 5 A. knockdown of SND1 by siRNA markedly inhibited CRC and GC cell proliferation, and miR-361-5p overexpression did not block cell proliferation in SND1 -depleted HCT116 or SW480 cells. [score:6]
A. knockdown of SND1 by siRNA markedly inhibited CRC and GC cell proliferation, and miR-361-5p overexpression did not block cell proliferation in SND1 -depleted HCT116 or SW480 cells. [score:6]
B. upregulation of SND1 promoted cell growth and abrogated miR-361-5p–induced growth inhibition in HCT116 or SW480 cells. [score:6]
Therefore, SND1 mRNA and protein expression in miR-361-5p -overexpressing or miR-361-5p -downregulated cells were investigated respectively. [score:6]
SND1 downregulates the miR-361-5p expression in CRC and GC cells. [score:6]
The result suggested that miR-361-5p inhibited SND1 expression via binding to the 3′-UTR of SND1. [score:5]
In contrast, the ectopic expression of SND1 vector that encoded the entire coding sequence of SND1 without its 3′-UTR markedly abrogated the tumor-suppressive effect induced by miR-361-5p (Figure 5C and 5D). [score:5]
CRC and GC cell lines infected with miR-361-5p expression vector or miR-361-5p inhibitior or NC were used in the following studies. [score:5]
In order to elucidate how SND1 inhibited the expression of miR-361-5p, we performed RIP experiments to precipitate SND1-bound RNAs. [score:5]
To probe the effect of the abnormal expression of miR-361-5p on tumor metastasis in vivo, control and miR-361-5p -overexpressed cells were injected into nude mice via the lateral tail vein. [score:5]
3) Overexpression of miR-361-5p markedly suppressed cell proliferation and invasion of cancer cells, which was partially rescued by SND1. [score:5]
Cells with relatively low miR-361-5p expression displayed a mesenchymal-like phenotype, and the expression of the mesenchymal marker (Vimentin) was enhanced. [score:5]
Because SND1 is one of the essential components of RISC which takes part in gene silencing and inhibits miRNA production [13], we next examined the effects of SND1 on miR-361-5p expression in HCT116 and MKN45 cells. [score:5]
Importantly, we also demonstrated that miR-361-5p is a downstream effector of SND1 because our interference experiments confirmed that miR-361-5p expression could be decreased by SND1 over -expression. [score:5]
As expected, miR-361-5p expression was inversely correlated with SND1 mRNA expression in the 10 CRC samples (r = −0.581, P = 0.023; Figure 4C). [score:5]
SND1 suppresses the expression of miR-361-5p. [score:5]
We showed that miR-361-5p contributed to CRC cell proliferation and participated in the induction of metastasis of CRC by suppressing the expression of SND1. [score:5]
The result was confirmed by histological staining and a statistical analysis, demonstrating that miR-361-5p over -expression strongly inhibited the ability of CRC cells to form metastases in the lung. [score:5]
Importantly, the expression level of miR-361-5p was negatively correlated with the expression of SND1. [score:5]
Interestingly, there was a marked change in the expression of hallmark EMT genes in miR-361-5p -expressing cells based on immunofluorescence staining (Figure 3C). [score:5]
It was found that co -expression of miR-361-5p markedly inhibited the firefly luciferase reporter activity of the wild-type SND1 3′-UTR, but did not change the activity of the mutant 3′-UTR constructs (Figure 4A). [score:5]
5) SND1 bounded with pre-miR-361-5p and suppressed the expression of miR-361-5p, thus exerting a feedback loop. [score:5]
Figure 3CRC and GC cell lines infected with miR-361-5p expression vector or miR-361-5p inhibitior or NC were used in the following studies. [score:5]
Additionally, a mutant SND1 3′ UTR reporter construct was made by site-directed mutagenesis in the putative target site of miR-361-5p using Quickchange XL site-directed mutagenesis kit (Agilent Technologies). [score:5]
Wound-healing assays indicated that the level of miR-361-5p expression was inversely correlated with the rates of wound healing: lower levels of miR-361-5p expression with faster healing (Figure 3A). [score:4]
Similarly, transwell assays with Matrigel demonstrated that HCT116 and MKN45 cells overexpressing miR-361-5p were found to have significantly lower rate of invasion than control cells, whereas SW480 cells expressing anti-miR-361-5p invaded faster (Figure 3B). [score:4]
In turn, SND1 activation significantly caused miR-361-5p down-regulation. [score:4]
The lentiviral expression vector expressing miR-361-5p precursor sequence was constructed using the following primer pairs: forward: 5′-GTGGGCATATgTgACCATCA-3′; reverse: 5′-TGAgCTCAACCATACCAggA-3′. [score:4]
To confirm that SND1 was directly inhibited by miR-361-5p, a dual-luciferase reporter system was used. [score:4]
1) miR-361-5p was down-regulated in CRC and GC cells and tissues in comparison to the controls. [score:4]
Firstly, cell proliferation assays revealed that miR-361-5p overexpression significantly reduced the growth rates of HCT116 and MKN45 cells, whereas silencing miR-361-5p expression significantly promoted the proliferation of SW480 cells (Figure 2A). [score:4]
We provided evidence that the multifunctional protein SND1 directly binds to the pre-miR-361-5p and reduces the expression of miR-361-5p. [score:4]
The present study is the first to demonstrate that miR-361-5p functions as a tumor-suppressive miRNA through directly binding to SND1 in CRC and GC. [score:4]
miR-361-5p decreases SND1 expression by directly binding to its 3′-UTR. [score:4]
In our study, we found that miR-361-5p was down-regulated in tumor tissues and cultured cells, increased cellular growth and invasion, and vice versa. [score:4]
The data were normalized and the luciferase activity of the control was set to 1. B. Effects of miR-361-5p dysregulation on endogenous SND1 expression which was analyzed by western blotting and RT-PCR. [score:4]
C. Association between miR-361-5p expression and survival of CRC patients. [score:3]
2) the expression levels of miR-361-5p exhibited a strongly negative association with lung metastasis and prognosis in clinical CRC patients. [score:3]
SND1 critically contributes to the cancer -inhibitory function of miR-361-5p. [score:3]
In situ hybridizationIn order to detect the expression of miR-361-5p in patients' tissues, in situ hybridization technique was used using Biochain kit (catalog#: K2191050; Biochain IsHyb In Situ hybridization kit) according to the manufacturer's protocol (Biochain and EXIQON). [score:3]
Based on these data, miR-361-5p could be a tumor suppressor miRNA in CRC and GC. [score:3]
So it strongly demonstrated that SND1 is a functional target of miR-361-5p. [score:3]
In order to detect the expression of miR-361-5p in patients' tissues, in situ hybridization technique was used using Biochain kit (catalog#: K2191050; Biochain IsHyb In Situ hybridization kit) according to the manufacturer's protocol (Biochain and EXIQON). [score:3]
Collectively, these data clearly demonstrate that miR-361-5p has a growth-suppressive function in CRC and GC. [score:3]
Cells were transfected with miR-361-5p mimics, NC in presence or absence of miR-361-5p inhibitor. [score:3]
miR-361-5p inhibits the invasion and metastasis of CRC and GC. [score:3]
After four weeks, eight mice were sacrificed and subcutaneous tumors were collected for analysis of the expression of SND1 and miR-361-5p. [score:3]
Altogether, these data not only associate miR-361-5p with growth and metastasis in CRC and GC, but also provide a new therapeutic target for treating CRC and GC. [score:3]
These data further indicated that SND1 could decrease the expression of miR-361-5p by forming SND1-pre-miR-361-5p complex, and consequently, exerted a negative feedback loop. [score:3]
Importantly, an in vivo tumor formation assay in a nude mouse mo del demonstrated that miR-361-5p overexpression significantly inhibited the tumorigenesis of CRC cells compared with the vector control (Figure 2D). [score:3]
SND1 attracted our attention because its 3′-UTR contains a putative target sequence for miR-361-5p (Figure 4A), and SND1 is closely involved in cancer cell migration and invasion [12]. [score:3]
6) In vivo studies showed that miR-361-5p significantly inhibited xenograft growth and invasion of tumors in nude mice. [score:3]
miR-361-5p suppresses CRC and GC cell growth in vitro and in vivo. [score:3]
In this study, we aimed to enlighten the significance of miR-361-5p in CRC and its potential target gene via a series of experiments in vitro and in vivo. [score:3]
miR-361-5p suppresses cancer cell proliferation in CRC and GC. [score:3]
Nude mice (n = 10 per group) were injected subcutaneously into opposite flanks with 1.5 × 10 [6] control cells and miR-361-5p -overexpressed cells. [score:3]
The relationship between the miR-361-5p level and SND1 expression was analyzed using Pearson's correlation. [score:3]
miR-361-5p suppresses invasion and metastasis of CRC and GC cells. [score:3]
Clinically, our analysis of 60 tumor samples from CRC patients revealed that low expression of miR-361-5p in CRC tissues was significantly correlated with advanced tumor stages, lung metastasis, and poor survival. [score:3]
Similar results were also found in the MKN45 with miR-361-5p overexpression (data not shown). [score:3]
C. The correlation between miR-361-5p and SND1 mRNA expression in 10 human CRC samples using quantitative PCR. [score:3]
C. Representative IF images indicated that miR-361-5p has an effect on the expression of EMT genes in CRC and GC cells. [score:3]
Taken together, these findings suggest that miR-361-3p strongly inhibits CRC and GC cell invasion and metastasis potentialities. [score:3]
miR-361-5p expression in human GC and CRC is decreased which is significantly correlated with poor survival. [score:3]
As shown in Figure 3D, the mice injected with the miR-361-5p -overexpressed CRC cells exhibited less visible metastatic nodules in the lung than the control group. [score:3]
Dual-luciferase 3′ UTR reporter assay was carried out to validate SND1 as a direct target of miR-361-5p. [score:3]
Kaplan-Meier survival test indicates that patients expressing low miR-361-5p levels exhibited significantly shorter survival (P = 0.014). [score:3]
Expression of miR-361-5p and its effect on CRC patients' survival. [score:3]
Furthermore, Kaplan–Meier analysis showed that the survival time of patients with low miR-361-5p expression was significantly shorter (Figure 1C). [score:3]
Representative staining images for miR-361-5p expression in CRC tissues and non-tumor colorectal tissues are shown (200 × magnification). [score:3]
D. Effects of miR-361-5p over -expression on tumor metastasis of indicated cells in nude mice (n = 10 per group): the number of metastatic nodules in the lung (left-panel); representative morphological observation of lung metastases (right-upper panel); and histopathological observation of lung sections (right-lower panel). [score:3]
SND1 mediates the tumor-suppressive function of miR-361-5p in CRC. [score:3]
D. Comparison of expression level of miR-361-5p between normal colorectal tissues and CRC cell lines using qRT-PCR assay. [score:2]
Interestingly, the consistent decreased expression of miR-361-5p was demonstrated in GC compared with normal gastric mucosa (Figure 1E). [score:2]
Cell-cycle assays also supported the results, because overexpression of miR-361-5p was found to be related to G1 cell-cycle arrest, which was evidenced by the reduced percentage of S and G2/M and the increased percentage of G1 (Figure 2C). [score:2]
4) SND1 was identified as a potential target of miR-361-5p in bioinformatics analysis and luciferase reporter assays. [score:2]
However, miR-361-5p knockdown increased cell growth but did not promote cell proliferation in SND1 -depleted HCT116 or SW480 cells. [score:2]
Recently, miR-361-5p emerged as an important regulator of tumorigenicity and cancer metastasis [7], however, its role in CRCs remains unknown. [score:2]
As shown in Figure 5A, on the one hand, siRNA -mediated SND1 silencing could phenocopy the proliferation-repressing effect of miR-361-5p, whereas anti-miR-361-5p could not restore cell proliferation in SND1 -depleted CRC cells. [score:1]
Another important discovery in this study is the forming of SND1-pre-miR-361-5p complex. [score:1]
Male Nu/Nu mice, obtained from the Experimental Animal Center of Shanghai Institute for Biological Sciences (SIBS), were injected subcutaneously with 1.5 × 10 [6] miR-361-5p or NC or anti-miR-361-5p or SND1 or SND1-siRNA or its control stable monoclonal cells to establish a CRC xenograft mo del. [score:1]
The level of SND1 mRNA was found to be higher in cancer tissues than in corresponding non-cancer tissue in which the level of miR-361-5p is high (Figure 4D). [score:1]
Thus, the miR-361-5p/SND1 feedback loop provides a new avenue to understand the mechanism of the tumor invasion and metastasis in CRC and GC. [score:1]
B. qRT-PCR assay showing that miR-361-5p expression is significantly decreased in a group of 60 CRC tissues when compared to matched normal tissues (P < 0.001). [score:1]
As shown in Figure 5C and 5D, silencing SND1 in CRC cells significantly decreased in vitro cell invasion and in vivo tumor metastasis, which was similar to the phenotype induced by miR-361-5p. [score:1]
B. The effect of miR-361-5p on colony formation in HCT116, SW480 and MKN45 cells. [score:1]
A. Analysis of miR-361-5p in situ hybridization (ISH) signal in CRC. [score:1]
HEK293 cells infected with anti-miR-361-5p lentivirus or negative control (NC) lentivirus were plated into 96-well plates. [score:1]
Next, we examined the effects of miR-361-5p on the ability of CRC and GC cells to invade and migrate. [score:1]
E. Relative expression of miR-361-5p in 5 gastric cancer cell lines compared with normal gastric mucosa using qRT-PCR assay. [score:1]
And the difference in miR-361-5p levels between SND1(Low) and SND1(High) patients with CRC (n = 60). [score:1]
These findings also provide an additional molecular mechanism of the pathophysiological functions of miR-361-5p and SND1. [score:1]
D. qRT-PCR analysis of bound pre-miR-361-5p in SND1 and EIF4A2 RIPs. [score:1]
However, only SND1, not EIF4A2, was confirmed as a protein binding with pre-miR-361-5p (Figure 6D). [score:1]
miR-361-5p mimics, scrambled miR-control, SND1 siRNA, or siRNA negative control were purchased from GenePharma (China), which were designed and chemically synthesised based on the following sequences: hsa-miR-361-5p mimics: 5′-ACGCCUGGAGAUUCUGAUAAUU-3′, negative control (NC): 5′-UUCUCCGAACGUGUCACGUTT-3′; SND1-specific siRNA: 5′-AAGGCATGAGAGCTAAT AATC-3′ (sense), 5′-AAGGAGCGATCTGCTAGCTAC-3′ (anti-sense), NC: 5′-UUCUCCGAACGUGUCACGUTT-3′ (sense), 5′-ACGUGACACGUUCGGAGAATT-3′ (anti-sense). [score:1]
Having observed the association of miR-361-5p expression and poor survival in CRC patients, we set out to functionally characterize the effects of miR-361-5p on CRC and GC cells. [score:1]
To further evaluate the function of miR-361-5p, it is important to determine an mRNA target of miR-361-5p that might mediate the role of miR-361-5p in tumorigenesis and invasion. [score:1]
The levels of miR-361-5p were also found to be significantly lower in CRC cell lines than in normal colorectal tissue (Figure 1D). [score:1]
The pre-miR361-5p plasmid (GFP-pre-miR-361-5p) was first transfected into HCT116 and MKN45 cells for 48 hours, the cells were then transfected with pSG5-SND1-Flag, pSG5 plasmid, SND1 siRNA, or scramble control, respectively. [score:1]
Consistent with previous studies, the present study indicates that SND1 is additionally involved in the processing of the precursors to the mature miRs of the miR-361-5p. [score:1]
The scatter diagram also demonstrated the decrease of miR-361-5p levels in CRC samples versus normal tissues, with an average 3.08-fold decrease (P = 0.004) (Figure 1B). [score:1]
Therefore, miR-361-5p may be highlighted as a novel agent for the treatment of patients with CRC and GC. [score:1]
HEK293 cells were cotransfected with a control vector or miR-361-5p and a luciferase reporter construct containing the wild-type or mutant SND1 3′-UTR. [score:1]
D. The effect of miR-361-5p on tumor formation in a nude mouse xenograft mo del. [score:1]
Reduction of miR processing was prevented when SND1 was silenced, indicating that SND1 is involved in the impairment of miR-361-5p maturation. [score:1]
Figure 4 A. Schematic representation of the luciferase reporter plasmids containing the SND1 3′-UTR and putative wild-type or mutant miR-361-5p -binding sequence in the 3′-UTR of SND1 mRNA. [score:1]
Figure 1 A. Analysis of miR-361-5p in situ hybridization (ISH) signal in CRC. [score:1]
A. Schematic representation of the luciferase reporter plasmids containing the SND1 3′-UTR and putative wild-type or mutant miR-361-5p -binding sequence in the 3′-UTR of SND1 mRNA. [score:1]
We went on to investigate that miR-361-5p inhibits CRC and GC cell invasion via biding to SND1. [score:1]
B. The expression of miR-361-5p in indicated cells was evaluated by RT-PCR. [score:1]
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[+] score: 124
Furthermore, our findings may also be applied in treating tumor angiogenesis since the overexpression of miR-361-5p suppressed cellular migration and vasculogenesis to levels similar to those achieved by EPCs treated with the Avastin anti-VEGF mAb, a clinically used target therapy drug (Figs. 1 & 3). [score:7]
These findings suggested that VEGF is an important direct downstream target of miR-361-5p, and the regulation of miR-361-5p/VEGF axis is unidirectional but not reciprocal. [score:6]
Although the 8 miRNAs we performed RT-qPCR validation were all up-regulated in disease EPCs, surprisingly only miR-361-5p and miR-484 were consistently more abundant in the plasma of CAD patients. [score:6]
0098070.g003 Figure 3(A) Overexpression of miR-361-5p in PB-EPCs down-regulated VEGF levels. [score:6]
Our research disclosed miR-361-5p suppresses EPC activities in CAD patients via targeting VEGF. [score:5]
Novel anti-miR361 -based therapeutic modalities may also be developed accordingly for targeting ischemia-related diseases. [score:5]
The direct targeting of VEGF by miR-361-5p was explored by luciferase reporter assays, and it was found that miR-361-5p repressed luciferase expression when the construct contained the VEGF 3′UTR fused downstream of the luciferase gene (Fig. 4A–B, the UTR-WT group). [score:5]
Suppression levels of miR-361-5p, not miR-484, restored VEGF expression and EPC functions. [score:5]
In contrast, miR-361-5p, alone with other microRNAs known to target VEGF directly, including miR-34a, miR-503 and miR-24, were dysregulated in CAD-EPCs (Fig. 2). [score:5]
Meanwhile, knockdown of miR-361-5p in diseased EPCs significantly improved blood flow recovery by 90% in the ischemic limbs in mice (Figures 5C–D; n = 6 per group). [score:4]
The lentiviral expression vector expressing miR-361-5p precursor sequence was constructed using the following primer pairs: forward: 5′-TTgggCATATgTgACCATCA-3′; reverse: 5′-ggAgCTCAACCATACCAggA-3′. [score:4]
By comparing the miRNA expression profiles between various EPCs with distinct angiogenic activities, we uncovered a significant miR-361-5p/VEGF axis for regulating EPC activities. [score:4]
miR-361-5p, but not miR-484, regulates EPC function via targeting VEGF. [score:4]
To over-express or knock down miR-361-5p and miR-484 in EPCs, agomir or antagomir were added into culture medium at a concentration of 50 nM at 70% to 80% cell confluence. [score:4]
Knock down of miR-361-5p, but not miR-484, in CAD-EPCs to a level compatible to that in healthy EPCs by oligonucleotide antagomirs restored VEGF expression (Fig. 3D and Fig. S1B). [score:4]
Overexpression of miR-361-5p, but not miR-484, resulted in the reduction of VEGF transcripts in healthy EPCs (Figs. 3A–B). [score:3]
0098070.g004 Figure 4(A) Structure of the VEGF transcript and the predicted binding site between the VEGF 3′UTR (untranslated region) and miR-361-5p. [score:3]
Figure S1 miR-361-5p, not miR-484, regulates EPC angiogenic activities via down -regulating VEGFA level. [score:3]
Of note, blocking VEGF activity did not affect the expression of miR-361-5p (Fig. 4C), and the addition of recombinant VEGF on CAD-EPCs did not either (Figs. S2C). [score:3]
miR-361-5p antagomirs were transfected into diseased EPCs 24 hours before transplantation, and the repression of miR-361-5p levels in transplanted EPCs at day 0 of injection were verified by RT-qPCR (Fig. 5B). [score:3]
To expand the clinical relevance and significance, we also examined the level of miR-361-5p in plasma from diseased individual to evaluate the potential of being a novel diagnostic biomarker for coronary artery disease. [score:3]
The expression levels of miR-361-5p were detected by RT-qPCR (left panel). [score:3]
Consistently, EPC motility was only inhibited in PB-EPCs transfected with miR-361-5p, but not those with miR-484 (Figs. 3B–C and Fig. S1A). [score:3]
CAD-EPCs with reduced miR-361-5p showed higher VEGF expression, better cellular motility, and superior tube formation ability (Fig. 4D, lanes 1 vs. [score:3]
, Guangzhou, China) for miR-361-5p or miR-484 are commercial synthetic RNA molecules with several chemical modifications for direct transfection without transfect reagents. [score:2]
miR-361-5p, but not miR-484, regulates EPC function via targeting VEGFWe then investigated the effects of miR-361-5p and miR-484 on VEGF levels and EPC activities. [score:2]
To further clarify the hierarchical relationship between miR-361-5p and VEGF, we compared the results of knocking down miR-361-5p to those of blocking VEGF activities (by adding the Avastin anti-VEGF mAb), either independently or in combination with miR-361-5p knockdown. [score:2]
Accordingly, it is possible to design new biomarker panels consisting of circulating miR-361-5p/-484 and miR-221/-222 for monitoring EPC activities in vitro or in vivo during the therapeutic procedure. [score:1]
Figure S2 VEGFA is a major downstream of miR-361-5p for regulaitng EPC acitivities. [score:1]
Further exploration of their levels in the plasma of CAD patient and control cases, only circulating miR-361-5p and miR-484 were more abundant in CAD cases by RT-qPCR (Fig. 2D). [score:1]
Consistently, microvasculature formation and cell proliferation abilities of miR-361-5p transfectants were also reduced significantly (Fig. 3C and Fig. S1A). [score:1]
0098070.g005 Figure 5Transplantation of miR-361-5p [low] CAD-EPCs improves blood perfusion in the ischemic hindlimb. [score:1]
Such repression could be reversed by mutating the predicted miR-361-5p -binding site (Fig. 4A–B, the UTR-Mut group). [score:1]
Here we show that miR-361-5p and miR-484 secreted by CAD-EPCs are more abundant in patient plasma (Fig. 2). [score:1]
Mice were randomly allocated to three groups (n = 6) with different treatments: EGM2 medium, CAD-EPC with scramble oligonucleotides, and CAD-EPC with miR-361-5p antagomirs (micrOFF, RiboBio Co. [score:1]
The limb ischemia mo del showed that blocking miR-361-5p restored the defective angiogenic activities of CAD-EPCs. [score:1]
Mice receiving miR-361-5p-repressed EPCs had more CD31+/PKH-26+ double -positive cells (white arrowheads) in ischemic muscle than another 2 control mice groups (Scr and medium). [score:1]
Finally, we evaluated the therapeutic potential of boosting the in vivo vasculogenesis/angiogenesis activity of diseased EPCs by blocking miR-361-5p. [score:1]
Transplantation of miR-361-5p [low] CAD-EPCs improves blood perfusion in the ischemic hindlimb. [score:1]
Because Avastin treatment is an approved therapy for metastatic colorectal cancer, metastatic kidney cancer, nonsquamous non–small cell lung cancer and glioblastoma, nucleic acid drugs such as synthetic miR-361-5p agomirs may become another choice for anti-VEGF therapy, in which its price should be cheaper than protein drugs. [score:1]
miR-361-5p promotes blood flow recovery in ischemic limbs in mice. [score:1]
2 & Figs. S2A–B; miR-361-5p levels detected by RT-qPCR were in Fig. 4C), whereas diminishing VEGF activities in miR-361-5p [low]/VEGF [high] CAD-EPCs abolished angiogenesis-related activities (Figs. 4C–D, lanes 2 vs. [score:1]
miR-361-5p and VEGF levels in treated CAD-EPCs were determined by RT-qPCR (C). [score:1]
The miR-361-5p/VEGF pair contributes to CAD-EPC activities. [score:1]
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[+] score: 49
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-125a, 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, 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
HDI Upregulates Selected miRNAs that Target AicdaWe have shown by qRT-PCR that miR-155, miR-181b, and miR-361, which silence AID by targeting Aicda 3′ UTR, were significantly upregulated by HDI (16). [score:11]
We have recently shown that HDI downregulated the expression of AID and Blimp-1 by upregulating miR-155, miR-181b, and miR-361, which silence Aicda mRNA, and miR-23b, miR-30a, and miR-125b, which silence Prdm1 mRNA, but not miR-19a/b, miR-20a, and miR-25, which are not known to regulate Aicda, Prdm1, or Xbp1 (16). [score:10]
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]
We have further shown that HDI, such as VPA and butyrate, inhibit AID and Blimp1 expression by upregulating miR-155, miR-181b, and miR-361, which silenced AICDA/Aicda mRNA, and miR-23b, miR-30a, and miR-125b, which silenced PRDM1/Prdm1 mRNA (16). [score:8]
We have shown by qRT-PCR that miR-155, miR-181b, and miR-361, which silence AID by targeting Aicda 3′ UTR, were significantly upregulated by HDI (16). [score:6]
Some miRNAs, including miR-155, miR-181b, and miR-361, can silence AID expression, whereas miR-30a and miR-125b can silence Blimp-1 expression (16). [score:5]
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[+] score: 31
The quantitative PCR results confirmed the expression of two most upregulated (hsa-miR-361-5p and hsa-miR-214) and downregulated (hsa-miR-1225-5p and hsa-miR-148a) miRNAs in the same 35 GC pairs (Figure 1B). [score:9]
Two most upregulated (hsa-miR-361-5p and hsa-miR-214) and two most downregulated (hsa-miR-1225-5p and hsa-miR-148a) miRNAs were further validated using qRT-PCR in GC tissue pairs. [score:7]
B. Validation of two most differentially upregulated (miR-214 and miR-361-5p) and downregulated (miR-148a and miR-1225-5p) miRNAs in tumor and corresponding nontumorous pairs used for microarray analysis. [score:7]
The average mRNA expression levels in cancerous tissues were increased by 2.81- and 1.92-fold (p < 0.01 for both) for hsa-miR-361-5p and hsa-miR-214, but decreased by 4.76- and 6.25-fold (p < 0.01 for both) for hsa-miR-148a and hsa-miR-1225-5p relative to those in the adjacent normal tissues. [score:3]
Consistently, in this study both miRNA array and quantitative PCR analysis showed that there was a significant increase in the level of miR-361-5p expression between GC tumors and their corresponding nontumorous tissues. [score:3]
MiR-361-5p was also often aberrantly expressed in some human cancers, such as cervical and prostate cancer [41, 42]. [score:2]
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[+] score: 24
Mir466i was upregulated in NLPs, while Mir7007, mmu-mir-703, Mir107, Mir361, Mir6918, Mir6982, and Mir3099 were downregulated in NLPs. [score:7]
microRNA-361 targets Wilms' tumor 1 to inhibit the growth, migration and invasion of non-small-cell lung cancer cells. [score:5]
MicroRNA-361-3p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC. [score:5]
MicroRNA-361-5p inhibits cancer cell growth by targeting CXCR6 in hepatocellular carcinoma. [score:4]
Among these miRNAs, Mir107 (Chen et al., 2013; Song et al., 2015; Xia et al., 2016; Yang et al., 2016) and Mir361 (Wu et al., 2013; Jacques et al., 2014; Chen et al., 2016; Sun et al., 2016) have been reported to suppress tumor growth and stem cell growth. [score:3]
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[+] score: 13
Mechanistically, the increased expression of miR-361-5p in diseased EPCs of coronary artery disease patients suppresses their angiogenesis capabilities by targeting VEGF expression [26]. [score:13]
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[+] score: 9
MiRNA target site/Species Human Mouse Cow Dog Chicken FrogTargeting Twist2 miR-15b-3p + − + + − − − miR-33-5p + + + + − + − miR-137-3p + + + + − + − miR-145a-5p + + + + − − + miR-151-5p + + + + − + − miR-214-5p + + + + − − − miR-326-3p + + + + − − − miR-337-3p + + + + − + − miR-361-5p + + + + − − − miR-378a-5p + + + + − − − miR-381-3p + + + + − + − miR-409-3p + + + + − − − miR-450b-5p + + + + − + − miR-508-3p + + + + − − − miR-543-3p + + + + − − − miR-576-5p + + + + − − − miR-580 + + + + − − − miR-591 + + + + − − − MicroRNAs underlined were tested in this study. [score:5]
The following miRNAs were tested for their potential to repress Twist1 translation in the human lung carcinoma cell line H1299: miR-33, miR-145a, miR-151, miR-326, miR-337, miR-361, miR-378a, miR-381, miR-409 and miR-543 (Fig. 1). [score:3]
The miRBase accession numbers for miRNAs are: mmu-miR-33 (MI0000707), mmu-miR-145a (MI0000169), mmu-miR-151 (MI0000173), mmu-miR-326 (MI0000598), mmu-miR-337 (MI0000615), mmu-miR-361 (MI0000761), mmu-miR-378a (MI0000795), mmu-miR-381 (MI0000798), mmu-miR-409 (MI0001160) and mmu-miR-543 (MI0003519). [score:1]
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[+] score: 7
Seven miRNAs (let-7e, miR-98, miR-361, miR-26b, miR-125a-5p, let-7i, and let-7f) were significantly up-regulated in the brain but down-regulated in the liver after RDX exposure. [score:7]
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[+] score: 6
Three miRNAs were expressed at levels more than 5-fold different between LAT Y136F CD4 [+] T cells and wild type CD4 [+] T cells undergoing homeostatic proliferation (miR-361, miR-139 and miR-125). [score:3]
In addition we can compose a list of other miRNAs that are differentially regulated more than 5-fold among various combinations of the three proliferative states: miR-96, miR-125a, miR-139, miR-148a, miR-155, miR-181a, miR-361, miR-466a/b and miR669f. [score:2]
H poly mmu-miR-150 mmu-miR-181a ↓↓ ↓↓ mmu-miR-669f ↓ ↓ mmu-miR-29c ↑ mmu-miR-155 ↑ ↑ mmu-miR-467f mmu-miR-466a/b-3p ↓ ↓ mmu-miR-361 ↑↑ ↓ mmu-miR-547 mmu-miR-1949 mmu-miR-345-3p ↓ ↑ mmu-miR-101b mmu-miR-340-5p mmu-miR-148a ↑ ↑ mmu-miR-139-5p ↓↓ ↓ mmu-miR-132 ↑ ↑ mmu-miR-539 ↓ mmu-miR-125a-5p ↑↑ ↑ ↓ mmu-miR-130b *miRNAs with Nanostring counts that passed the minimum intensity filter and have >2-fold differences among any two-way comparison. [score:1]
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[+] score: 5
Other miRNAs from this paper: hsa-let-7f-1, hsa-let-7f-2, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-32, mmu-mir-1a-1, mmu-mir-133a-1, mmu-mir-134, mmu-mir-135a-1, mmu-mir-144, mmu-mir-181a-2, mmu-mir-24-1, mmu-mir-200b, mmu-mir-206, hsa-mir-208a, mmu-mir-122, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-181a-1, hsa-mir-214, hsa-mir-200b, mmu-mir-299a, mmu-mir-302a, hsa-mir-1-2, hsa-mir-122, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-144, hsa-mir-134, hsa-mir-206, mmu-mir-200a, mmu-mir-208a, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-24-2, mmu-mir-328, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-25, mmu-mir-32, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-214, mmu-mir-135a-2, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-200a, hsa-mir-302a, hsa-mir-299, hsa-mir-361, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, hsa-mir-377, mmu-mir-377, hsa-mir-328, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, hsa-mir-20b, hsa-mir-429, mmu-mir-429, hsa-mir-483, hsa-mir-486-1, hsa-mir-181d, mmu-mir-483, mmu-mir-486a, mmu-mir-367, mmu-mir-20b, hsa-mir-568, hsa-mir-656, mmu-mir-302b, mmu-mir-302c, mmu-mir-302d, mmu-mir-744, mmu-mir-181d, mmu-mir-568, hsa-mir-892a, hsa-mir-892b, mmu-mir-208b, hsa-mir-744, hsa-mir-208b, mmu-mir-1b, hsa-mir-302e, hsa-mir-302f, hsa-mir-1307, eca-mir-208a, eca-mir-208b, eca-mir-200a, eca-mir-200b, eca-mir-302a, eca-mir-302b, eca-mir-302c, eca-mir-302d, eca-mir-367, eca-mir-429, eca-mir-328, eca-mir-214, eca-mir-200c, eca-mir-24-1, eca-mir-1-1, eca-mir-122, eca-mir-133a, eca-mir-144, eca-mir-25, eca-mir-135a, eca-mir-568, eca-mir-133b, eca-mir-206-2, eca-mir-1-2, eca-let-7f, eca-mir-24-2, eca-mir-134, eca-mir-299, eca-mir-377, eca-mir-656, eca-mir-181a, eca-mir-181b, eca-mir-32, eca-mir-486, eca-mir-181a-2, eca-mir-20b, eca-mir-361, mmu-mir-486b, mmu-mir-299b, hsa-mir-892c, hsa-mir-486-2, eca-mir-9021, eca-mir-1307, eca-mir-744, eca-mir-483, eca-mir-1379, eca-mir-7177b, eca-mir-8908j
Most of these serum-specific miRNAs were expressed in both breeds (Warmbloods and ponies), although we identified two miRNAs expressed solely in Warmblood (eca-let-7f, eca-miR-361-5p) and 20 other solely in ponies (Fig.   6d). [score:5]
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[+] score: 4
miR-361-regulated prohibitin inhibits mitochondrial fission and apoptosis and protects heart from ischemia injury. [score:4]
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[+] score: 3
MiR-361-regulated prohibitin inhibits mitochondrial fission and apoptosis and protects heart from ischemia injury. [score:3]
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[+] score: 3
A combination of miR-17, miR-20a, miR-106a, and miR-376c indicated a high level of accuracy for detecting H7N9 viral infection 30, and an altered expression pattern of miR-361-5p, miR-899, and miR-576-3p was reported to distinguish patients with pulmonary tuberculosis from healthy people 28. [score:3]
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[+] score: 3
After normalizing the expression levels with the corresponding geometric mean value of the reference genes U6 snRNA, mmu-miR-191, mmu-miR-423-5p, mmu-miR-361 and mmu-miR-103, the samples were checked for outliers to be excluded. [score:3]
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[+] score: 3
Using the Patrocles database, we found polymorphic miRNA target sites for bta-miR-199b, -miR-199a-5p, and -miR-361 in the IL1B gene and for –miR-126 in the CYP11B1 gene. [score:3]
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[+] score: 3
Many miRNAs that were shown to have altered expression in previous studies of male infertility, including hsa-miR-30c-1 [12], hsa-mir-34b [13], mir-371 [14], hsa-mir-29c [13], and miR-361 [15], were also enriched in our study. [score:3]
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[+] score: 2
Individual TaqMan assays (Applied Biosystems) were used to analyse the expression of the following mature mouse miRNAs: miR-181c, miR-9, miR-20b, miR-21, miR-30c, miR-148b, miR-361, miR-409-3p and Let-7i. [score:2]
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[+] score: 2
Figure 2A shows the difference in the mapping of the four selected mouse miRNAs (mmu-miR-124, mmu-miR-153, mmu-miR-361 and mmu-miR-98; only four miRNAs were selected for simplicity). [score:1]
The results of miRror2.0 for the input of mmu miR-98, mmu miR-124, mmu miR-153 and mmu miR-361 are shown. [score:1]
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[+] score: 1
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-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-93, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-107, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-23b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-101a, mmu-mir-124-3, mmu-mir-125a, mmu-mir-130a, mmu-mir-9-2, mmu-mir-135a-1, mmu-mir-136, mmu-mir-138-2, mmu-mir-140, mmu-mir-144, mmu-mir-145a, mmu-mir-146a, mmu-mir-149, mmu-mir-152, mmu-mir-10b, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-185, mmu-mir-24-1, mmu-mir-191, mmu-mir-193a, mmu-mir-195a, mmu-mir-200b, mmu-mir-204, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, 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-204, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-200b, mmu-mir-301a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-130b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-130a, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-138-2, hsa-mir-140, hsa-mir-144, hsa-mir-145, hsa-mir-152, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-136, hsa-mir-138-1, hsa-mir-146a, hsa-mir-149, hsa-mir-185, hsa-mir-193a, hsa-mir-195, hsa-mir-320a, 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-16-1, mmu-mir-16-2, mmu-mir-20a, mmu-mir-23a, mmu-mir-24-2, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-93, mmu-mir-34a, mmu-mir-330, mmu-mir-339, mmu-mir-340, mmu-mir-135b, mmu-mir-101b, hsa-mir-200c, hsa-mir-181b-2, mmu-mir-107, mmu-mir-10a, mmu-mir-17, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-320, mmu-mir-26a-2, mmu-mir-221, mmu-mir-222, mmu-mir-29b-2, mmu-mir-135a-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-361, hsa-mir-376a-1, mmu-mir-376a, hsa-mir-340, hsa-mir-330, hsa-mir-135b, hsa-mir-339, hsa-mir-335, mmu-mir-335, mmu-mir-181b-2, mmu-mir-376b, mmu-mir-434, mmu-mir-467a-1, hsa-mir-376b, hsa-mir-485, hsa-mir-146b, hsa-mir-193b, hsa-mir-181d, mmu-mir-485, mmu-mir-541, hsa-mir-376a-2, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, mmu-mir-301b, mmu-mir-674, mmu-mir-146b, mmu-mir-467b, mmu-mir-669c, mmu-mir-708, mmu-mir-676, mmu-mir-181d, mmu-mir-193b, mmu-mir-467c, mmu-mir-467d, hsa-mir-541, hsa-mir-708, hsa-mir-301b, mmu-mir-467e, mmu-mir-467f, mmu-mir-467g, mmu-mir-467h, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, mmu-mir-467a-2, mmu-mir-467a-3, mmu-mir-467a-4, mmu-mir-467a-5, mmu-mir-467a-6, mmu-mir-467a-7, mmu-mir-467a-8, mmu-mir-467a-9, mmu-mir-467a-10, hsa-mir-320e, hsa-mir-676, mmu-mir-101c, mmu-mir-195b, mmu-mir-145b, mmu-let-7j, mmu-mir-130c, mmu-mir-30f, mmu-let-7k, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
50E-0367mmu-miR-339-5pmir-3390.206.807.92E-037.53E-028mmu-miR-34c-5pmir-340.246.689.54E-066.88E-0477mmu-miR-34a-5pmir-340.179.541.17E-029.66E-0245mmu-miR-340-5pmir-3400.178.511.71E-032.45E-0217mmu-miR-361-5pmir-3610.247.887.74E-052.90E-0319mmu-miR-376b-3pmir-3680.268.451.05E-043.50E-0356mmu-miR-376a-3pmir-3680.1910.215.63E-036.40E-0223mmu-miR-434-3pmir-4340.2210.461.76E-044. [score:1]
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