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79 publications mentioning mmu-mir-135b

Open access articles that are associated with the species Mus musculus and mention the gene name mir-135b. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 306
More importantly, forced expression of miR-135b into GSCs markedly suppressed proliferation, motility and invasion of glioma cells as well as their stem cell-like phenotype through targeting ADAM12, SMAD5 and GSK3β. [score:7]
The comparison in GSCs between the expression of miR-135b and the protein level of the three targets showed an inverse correlation (Figure 4A and Supplementary Figure S7), thus supporting the hypothesis that ADAM12, SMAD5 and GSK3β are indeed miR-135b targets in GSCs. [score:7]
Moreover, a third miR-135b target in GSCs could be GSK3β, whose downregulation has been involved in radioresistance acquisition of a U87MG GBM cell line derivative [29]. [score:6]
More recently, it has been demonstrated that miR-135b expression is frequently upregulated in osteosarcoma and promotes cell proliferation, migration and invasion [13]. [score:6]
These results strongly support a direct targeting of ADAM12 by miR-135b as previously demonstrated for the other two targets SMAD5 and GSK3β [28, 29]. [score:6]
A list of potential target mRNAs was obtained for miR-135b using TargetScan 6.2 algorithm (www. [score:5]
miR-135b overexpression induces a significant decrease in the level of target proteins. [score:5]
Thus, miR-135b restoration resulted in a considerable inhibition of proliferation, migration and colony formation of all the GSCs tested, suggesting that this miRNA could play a pivotal role in GBM oncosuppression. [score:5]
A. Normalized levels of miR-135b/U6 expression were plotted with protein levels of the three main miR-135b targets in a large cohort of GSCs, T98G GBM cell line and a representative normal neural stem cell line. [score:5]
The results shown in Figure 5B-5D support the hypothesis that ADAM12 contributes to the oncosuppressive properties of miR-135b, as its re -expression mitigates the decreased proliferation (Figure 5B), migration (Figure 5C) and clonogenic ability (Figure 5D) imparted by this miRNA. [score:5]
No significant induction of apoptosis was observed in both GSC lines (Supplementary Figure S2b) suggesting that overexpression of miR-135b is able to impairs GSC cell growth mainly by inhibiting cell proliferation rather than increasing apoptosis. [score:5]
Figure 4 A. Normalized levels of miR-135b/U6 expression were plotted with protein levels of the three main miR-135b targets in a large cohort of GSCs, T98G GBM cell line and a representative normal neural stem cell line. [score:5]
Our data on the role of miR-135b in GBM along with recent progress in the delivery of functional miRNA molecules across the blood-brain barrier [47], reinforce the concept that molecular -targeting therapy based on miRNA expression in GSCs has the potential to allow more effective treatment strategies for this incurable type of cancer. [score:5]
Another potential mediator of the tumor-suppressive ability of miR-135b is SMAD5, which has been recently identified as one of the target of miR-135b activated by the transcription factor PAX6 [28]. [score:5]
To further understand the molecular mechanism by which miR-135b can behave as tumor-suppressor, we tried to establish whether any of its putative targets might play a significant role in GBM biology. [score:5]
In line with this evidence, we observed that miR-135b expression is coupled to a significant decrease in the expression of SDC4 and β1 integrin transcripts, along with other ligands and receptors of the ECM. [score:5]
miR-135b showed the most homogeneous profile in the GSC lines analyzed among the most downregulated miRNAs (Figure 1A). [score:4]
miR-135b is frequently amplified and upregulated in hepatocellular carcinoma (HCC) and promotes HCC invasion and metastasis [12]. [score:4]
We identified ADAM12 and confirmed SMAD5 and GSK3β as direct targets of miR-135b. [score:4]
miR-135b is downregulated in GSC lines. [score:4]
The luciferase activity was restored in a construct bearing five mutations in the putative miR-135b target sequence (Supplementary Figure S8). [score:4]
To assess whether ADAM12 is a direct target of miR-135b, we cloned part of ADAM12 3′UTR into a luciferase reporter vector. [score:4]
As shown in Figure 1B, these cell lines express very low levels of miR-135b compared to normal neural stem-like cells, consistent with the expression in the majority of GSC lines. [score:4]
Compared to 4 normal brain tissues, derived from patient deceased for non oncological causes, GBM samples showed a slight but not significant increase of miR-135b expression, whereas GSCs, even though with a less homogeneous distribution, displayed a higher expression of miR-135b. [score:4]
Bars indicate the mean values ± SD of two independent experiments and show a significant inverse correlation among miR-135b and putative target levels (ADAM12 ρ = −0.635, p = 0.001; SMAD5 ρ = −0.484, p=0.022; GSK3β ρ = −0.447, p = 0.037). [score:3]
This led us to assess the overall transcriptome changes upon enforced miR-135b expression in GSC lines, observing the modulation of transcripts belonging to additional pathways that play a relevant role in tumorigenesis. [score:3]
To further confirm the data on miR-135b expression, we analyzed by In Situ Hybridization (ISH) a panel of 12 GBM specimens and 4 normal brains derived from patients deceased for non oncological causes (Supplementary Figure S1c). [score:3]
In this report, we describe miR-135b as a miRNA that is significantly downregulated in GSCs compared to normal adult neural stem cells. [score:3]
Both patients and normal brains showed a highly heterogeneity of miR-135b expression ranging from complete negativity (Supplementary Figure S1c, panel D), few scattered positive cells (panel E) to more abundant positivity (panel C and F) with no significant differences between normal and GBM samples. [score:3]
Moreover, miR-135b has been proposed as a biomarker and potential therapeutic target for colorectal cancer (CRC) and advanced adenoma [11]. [score:3]
Transcriptome changes associated with miR-135b expression. [score:3]
To ascertain whether a decrease in ADAM12 mediates the oncosuppressor properties of miR-135b and to verify phenotype recovery, functional experiments were performed. [score:3]
Interestingly, in GSC #74, differently from the other transduced GSC lines, no increase of pre-G [0] peak was found and a block in G [2]/M phase was observed, suggesting that miR-135b could inhibits tumor cell proliferation through different mechanisms. [score:3]
B. Growth curve of GSC lines #83 and #144P (TRIPZ and TRIPZ-miR-135b) expressing ADAM12 gene. [score:3]
To further investigate the role of miR-135b on GCS tumorigenic properties we over-expressed miR-135b in GSC lines by using an inducible Tet-On lentiviral vector (TRIPZ) carrying pri-miR-135b in the 3′ untranslated region of Red Fluorescent Protein (RFP). [score:3]
miR-135b overexpression reduces the in vivo growth of GSC-derived brain tumor. [score:3]
Particularly, the overexpression of miR-135b has been described in human head and neck squamous cell carcinoma (HNSCC) cell lines, where it causes increased cell proliferation, migration, and colony formation [8]; in human breast cancers, where it correlates with patient survival and early metastatization [9]; in highly invasive non-small-cell lung cancer cells where promotes cancer metastasis [10]. [score:3]
The expression of miR-135b in GSCs could be due to different mechanisms including the EGF machinery and microenvironment [34]. [score:3]
In contrast to this view, we here describe that miR-135b is highly downregulated in our GSC line collection compared to their normal neural stem cells. [score:3]
Restoration of miR-135b impairs tumorigenic properties of GSCs in vitroTo further investigate the role of miR-135b on GCS tumorigenic properties we over-expressed miR-135b in GSC lines by using an inducible Tet-On lentiviral vector (TRIPZ) carrying pri-miR-135b in the 3′ untranslated region of Red Fluorescent Protein (RFP). [score:3]
The miR-135b precursor was cloned in the 3′ untranslated (UTR) region of RFP in the pTRIPZ doxycycline inducible lentiviral vector (Thermo Fisher Scientific, Waltham, MA, USA). [score:3]
We hypothesized that this decrease in proteins involved in cell/extracellular matrix (ECM) interaction might contribute to the proliferation and migration inhibition exerted by miR-135b both by diminishing integrin -mediated signaling and by reducing EGF and FGF2 effects. [score:3]
miR-135b expression is decreased in human GSC lines. [score:3]
Thus, restoration of miR-135b expression significantly impairs GSC tumorigenic ability in vitro and in vivo. [score:3]
To corroborate these results, we evaluated the expression of the three target proteins in TRIPZ and TRIPZ-miR-135b GSCs. [score:3]
C. Analysis of the extent of tumor cell mass in the full series of brain sections from mice injected with control and miR-135b -overexpressing GSCs. [score:3]
Moreover, we analyzed the clonogenic capability of GSC expressing miR-135b. [score:3]
miR-135b overexpression reduces cell growth, migration and clonogenic abilities of GSCs. [score:3]
Microarray profiling allowed to find additional genes in the TGFβ pathway that are downmodulated in miR-135b expressing cells, such as SMAD2 and TGFBR2 (Supplementary Figure S9). [score:3]
We expected higher effect of miR-135b restoration in this GSC line since it has the lowest expression of miR-135b. [score:3]
B. Expression of miR-135b detected by real-time PCR in a large collection of GSCs (grey), human neural adult (green) and fetal (blue) stem cells and GBM cell lines (purple). [score:3]
Furthermore, a low expression of miR-135b was confirmed in a panel of 16 GBM samples, 11 of which derived from patients that gave raise to GSC cultures (Supplementary Figure S1a, left panel). [score:3]
Seven GSC lines (#1, #30P, #61, #74, #83, #83.2 and #144P) chosen as representatives of different levels of miR-135b expression, were transduced and exposed to doxycycline. [score:3]
To complement this set of experiments, endogenous miR-135b was inhibited in normal neural adult stem cells by transducing lentiviral vector carrying anti-sense miR-135b or anti-sense control sequence and green fluorescent protein (GFP) as a reporter. [score:3]
Xenograft experiments, indeed, showed that tumor generated by GSC injection expressed lower level of miR-135b than the parental cell line, comparable with GBM samples. [score:3]
Moreover, miR-135b expression in GBM samples was markedly lower than in colon adenocarcinoma used as the positive control (panel A). [score:3]
TRIPZ- and TRIPZ-miR135b GSC #83 and #144P were transduced with lentiviral constructs to restore ADAM12 target gene. [score:3]
Ectopic expression of miR-135b significantly impaired cell growth of all the GSC lines tested (Figure 2B), with a stable decrease in growth rate. [score:3]
Tumor-suppressor function of miR-135b involved ADAM12 and SMAD5 signaling. [score:3]
The first evidence of a correlation between miR-135b and cancer emerged from a global miRNA expression profiling of microdissected tissues from pancreatic ductal adenocarcinoma (PDAC) patients that identified miR-135b as a novel biomarker for this tumor type [7]. [score:3]
in) were used for miR-135b target prediction. [score:3]
Results in Figure 4B show that ADAM12, SMAD5 and GSK3β target proteins are considerably diminished in cells after miR-135b is induced, albeit at different extent that might arise from differential affinity of the miRNA for the transcript, differential transcript/protein half-life or other factors. [score:3]
Furthermore, our data show that miR-135b inhibits glioma tumorigenesis and invasion in the brain of mice. [score:3]
B. Representative western blot analyses of the three main miR-135b targets in a cohort of GSCs transduced with either TRIPZ vector or TRIPZ-miR-135b. [score:3]
Being this observation apparently in contradiction with those published so far, we verified miR-135b expression in a larger panel of GSCs, as well as in the primary TB10, and commercially available T98G and U87MG, GBM cell lines (Figure 1B). [score:3]
miR-135b significantly reduced BrdU incorporation in both cell lines independently of the levels of endogenous and restored miRNA expression (Supplementary Figure S2a) indicating a decreased progression in the cell cycle through the S phase. [score:3]
Both GSCs and GBM samples, expressed lower level of miR-135b compared to normal neural stem cell reference. [score:2]
miR-135b knockdown induced only minimal variations in either estimate stem cell frequency (32.4 of anti-miR-135b vs 45.3 of NTC, p = 0.317), or BrdU incorporation (Supplementary Figure S4b) or migration (Supplementary Figure S4c). [score:2]
All GSC lines transduced with this vector showed miR-135b expression levels comparable to normal cells or increased when compared to control vector (TRIPZ)-transduced cells. [score:2]
To gain further insight into the regulatory program of miR-135b in GSCs, we assessed the transcriptome variation upon miR-135b doxycycline -mediated induction. [score:2]
Moreover, TUNEL assay did not show an increase of cell death in TRIPZ-miR-135b xenografts (data not shown) confirming that, as assessed in vitro, miR-135b exerts its function mainly by inhibiting proliferation than by inducing apoptosis. [score:2]
To better characterized the inhibitory effect of miR-135b restoration on cell proliferation, we performed BrdU incorporation assay on 2 out of 7 cell lines, GSC #83, chosen as it shows the lowest ectopic expression of miR-135b, and GSC #144P, representative of the average levels achieved after transduction (Figure 2A). [score:2]
The analysis of miR-135b expression in GBM tissue samples showed a slight but not significant, increase compared to normal brain tissue however, in both tissue samples, miR-135b levels were lower than in cell cultures. [score:2]
These results may be consistent with the relative small changes of miR-135b after knockdown of endogenous miR-135b. [score:2]
Further studies revealed that dysregulation of miR-135b has a critical role in cancer progression. [score:2]
miRZip™ anti-sense miR-135b and miRZip™ control (NTC) were purchased by SBI (System Biosciences Inc. [score:1]
D. Analysis of migration efficiency in GSCs transduced with miR-135b 48h after induction. [score:1]
Decreased miR-135b and miR-21 levels were observed in both xenograft mo dels as compared to cultured tumor generating GSCs, indicating that microenvironment may contribute to miRNA regulation. [score:1]
To this end, we performed microarray analysis of RNA from TRIPZ and TRIPZ-miR-135b GSC cell line #83. [score:1]
C. Cell cycle phase distribution in TRIPZ and TRIPZ-miR-135b GSCs 6 days after induction. [score:1]
We then examined whether miR-135b could alter additional malignant features of GSCs, such as migration. [score:1]
293T were transiently co -transfected by Lipofectamine 2000 (Life Technologies Corporation) with 0.8 μg of firefly luciferase reporter plasmid containing wild-type or mutated ADAM12 3′UTRs, 40 pmol of either the hsa-miR135b mimic or control -mimic oligonucleotides (Ambion, Life technologies) and with 50 ng of Renilla luciferase pRL-TK as normalizer. [score:1]
Relative expression was calculated with relative standard curves for miR-135b and the endogenous control. [score:1]
TRIPZ and the TRIPZ-miR-135b U87MG GBM line were grafted into the striatum of NOD/SCID mice. [score:1]
E. Analysis of efficiency in colony formation of GSCs after transduction with TRIPZ-miR-135b. [score:1]
The motility of GSCs after miR-135b induction was examined and a dramatic reduction in the migration capabilities of TRIPZ-miR-135b GSCs (Figure 2D and Supplementary Figure S3), was observed. [score:1]
After transduction a 40% decrease of the endogenous levels of miR-135b was observed in GFP -positive cells (Supplementary Figure S4a). [score:1]
Values below the miR-135b lanes indicate the fold change in protein levels relative to the TRIPZ control vector. [score:1]
In situ detection of miR-135b was performed on formalin fixed paraffin embedded GBM samples using miRCURY LNA microRNA ISH optimization kit (Exigon, Vedbaek Denmark) according to manufacturer's instruction. [score:1]
To confirm the effect of miR-135b restoration in tumor growth we chose subcutaneous grafting of GSCs as Matrigel implants in immunodeficient mice, a well suited mo del to study the early stages of in vivo tumor growth [25]. [score:1]
A. of ADAM12 on GSC lines #83 and #144P (TRIPZ and TRIPZ-miR-135b) transduced with either empty Tween vector or Tween-ADAM12. [score:1]
C. Percentage of migrating cells in GSC (TRIPZ and TRIPZ-miR-135b) after transduction with either Tween or Tween-ADAM12 vectors. [score:1]
Analysis of variance demonstrated a significant effect of miR-135b restoration on the ability of GSCs to migrate (p < 0.0001). [score:1]
Eight weeks after grafting, control TRIPZ grafted mice (n = 6) harbored tumors that invaded the homolateral striatum, piriform cortex, corpus callosum, anterior commissure, internal capsule, and fimbria-hippocampus, whereas the degree of brain invasion was significantly reduced in TRIPZ-miR-135b grafted mice (n = 6) (Figure 3C). [score:1]
miR-135b restoration significantly decreases in vivo tumor growth. [score:1]
Since recent evidence supports the notion that miRNAs act on their target gene repertoire also at the transcriptional level affecting the transcript stability [26], we characterized at the transcriptome level the effects of miR-135b restoration in the context of GSC cell lines. [score:1]
In situ hybridization In situ detection of miR-135b was performed on formalin fixed paraffin embedded GBM samples using miRCURY LNA microRNA ISH optimization kit (Exigon, Vedbaek Denmark) according to manufacturer's instruction. [score:1]
A. levels of miR-135b in GSCs non-transduced and transduced with either TRIPZ or TRIPZ-miR-135b inducible vectors after doxycycline exposure and in NS5 normal neural stem cell line. [score:1]
Subcutaneous implant of T98G GBM cells was performed by injecting 5×10 [5] TRIPZ and TRIPZ-miR-135b T98G cells mixed with 0.1 ml of cold Matrigel. [score:1]
Fluorescence microscopy analysis of serial coronal brain sections showed that the degree of brain invasion was significantly reduced in TRIPZ-miR-135b GSC brain xenografts (Figure 3B). [score:1]
Figure 2 A. levels of miR-135b in GSCs non-transduced and transduced with either TRIPZ or TRIPZ-miR-135b inducible vectors after doxycycline exposure and in NS5 normal neural stem cell line. [score:1]
In brain tumors miR-135b expression has been shown to be significantly higher in GBM compared to lower grade gliomas [14] as well as in frankly tumoral compared to peritumoral areas of GBM samples [15]. [score:1]
Altogether, these data strongly suggest that miR-135b behaves as an onco-miRNA promoting tumor cells proliferation and invasion or as a key downstream effector of oncogenic pathways promoting tumor transformation and progression. [score:1]
B. Growth curves of individual GSCs (line number on top of each plot) transduced with either TRIPZ or TRIPZ-miR-135b vectors. [score:1]
Analysis of variance demonstrated a significant effect of the presence of miR-135b on the colony-forming ability of GSCs (p < 0.0001). [score:1]
Mice were injected with two different GSC lines (#83 and #144P) transduced with either empty vector or miR-135b. [score:1]
A similar pattern was found in GSC #144P xenografts with invasion volumes of 2.172 ± 0.235 and 1.301 ± 0.194 mm [3] (mean ± sem) in TRIPZ and TRIPZ-miR-135b grafted mice, respectively (p = 0.046) (Figure 3C). [score:1]
For intracranial implantation of U87MG GBM cells, male NOD-SCID mice were implanted intracranially with 0.2 × 10 [5] TRIPZ and TRIPZ-miR-135b U87MG cells resuspended in 4 μl of serum-free DMEM. [score:1]
RFP -positive cells were flow-sorted and miR-135b restoration was confirmed by real-time PCR (Figure 2A). [score:1]
D. Analysis of efficiency in colony formation of GSC (TRIPZ and TRIPZ-miR-135b) after transduction with Tween or Tween-ADAM12 vectors. [score:1]
In mice injected with GSC #83, the volume of the brain region invaded by the red fluorescent tumor cells was 2.597 ± 0.365 and 1.376 ± 0.187 mm [3] (mean ± sem) in TRIPZ and TRIPZ-miR-135b grafted mice, respectively (p = 0.041). [score:1]
Even though a pro-tumorigenic function has been described for miR-135b in different cellular systems, functional characterization of this miRNA in GSC showed a tumor suppressive behavior. [score:1]
2×10 [5] TRIPZ and TRIPZ-miR-135b GSCs, were intracranially injected into male NOD/SCID mice (n, 6; 4-6 weeks of age; CD1 NOD-/SCID mice, Charles Rives, Italy). [score:1]
Conversely, the brains grafted with TRIPZ-miR-135b U87MG cells (n = 4) showed groups of fluorescent cells in the injected area that did not produced any mass effect on the surrounding brain parenchyma (Supplementary Figure S5, lower panel) and with no evidence of proliferating activity. [score:1]
Restoration of miR-135b impairs tumorigenic properties of GSCs in vitro. [score:1]
Thus, to evaluate micro environmental effects on miR-135b expression mouse xenogenic tumor by intracranial and subcutaneous injection of GSCs were generated (Supplementary Figure S1b). [score:1]
Briefly, total RNA was extracted from TRIPZ and TRIPZ-miR-135b GSC#83 transduced cells. [score:1]
Figure 5 A. of ADAM12 on GSC lines #83 and #144P (TRIPZ and TRIPZ-miR-135b) transduced with either empty Tween vector or Tween-ADAM12. [score:1]
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[+] score: 241
Other miRNAs from this paper: hsa-mir-135b
Here, we demonstrated that miR-135b-5p expression was downregulated in human osteoblastoma tissues, which was associated with Ppm1e upregulation.-5p silenced Ppm1e and potently inhibited osteoblastoma cell proliferation in vitro and in vivo. [score:11]
If Ppm1e is the direct target of miR-135b-5p, knockdown of Ppm1e shall also inhibit osteoblastoma cell proliferation. [score:7]
miR-135b-5p upregulation correlates with Ppm1e upregulation and AMPKα1 de-phosphorylation in human osteoblastoma tissues. [score:7]
miR-135b-5p was upregulated in Vec-miR-135b -expressing tumors (Figure 6F). [score:6]
Therefore, miR-135b-5p expression was in-effective when Ppm1e was depleted, suggesting that Ppm1e is the direct target of this Anti-oncomir. [score:6]
On the other hand, miR-135b-5p's target, Ppm1e mRNA, was upregulated in osteoblastoma tissues (Figure 1B). [score:6]
qRT-PCR results in Figure 2A demonstrated that expression level of miR-135b-5p was indeed significantly upregulated in the stable cells (“L1/L2/L3”). [score:6]
As demonstrated, miR-135b-5p expression level was significantly downregulated in osteoblastoma tissues (“Tumor”, n = 10), as compared to that in the surrounding normal bone tissues (“Normal”, n = 10) (Figure 1A). [score:5]
Stable MG-63 cells (A– C) or U2OS cells (D– F), expressing miR-135b vector (“Vec-miR-135b”, three lines each, “L1/L2/L3”), microRNA control (“mi-C”) vector or the empty vector (“Vec”, pSuper-puro), were subjected to qRT-PCR assay to test expression of miR-135b-5p (A and D) and Ppm1e mRNA (B and E); Listed proteins in above cells were tested by Western blot assay, Ppm1e protein expression (vs. [score:5]
Figure 2Stable MG-63 cells (A– C) or U2OS cells (D– F), expressing miR-135b vector (“Vec-miR-135b”, three lines each, “L1/L2/L3”), microRNA control (“mi-C”) vector or the empty vector (“Vec”, pSuper-puro), were subjected to qRT-PCR assay to test expression of miR-135b-5p (A and D) and Ppm1e mRNA (B and E); Listed proteins in above cells were tested by Western blot assay, Ppm1e protein expression (vs. [score:5]
Remarkably, miR-135b-5p -induced MG-63 cell proliferation inhibition was almost reversed by AMPKα1 knockdown or mutation (Figure 5C and 5D). [score:5]
Intriguingly, we here proposed that Ppm1e is the primary target of miR-135b in mediating its inhibition against osteoblastoma cells. [score:5]
First, we tested expression of miR-135b-5p, the Ppm1e -targeting miRNA [19, 20], in human osteoblastoma tissues. [score:5]
Above results showed that forced -expression of miR-135b-5p activated AMPK signaling and inhibited osteoblastoma cell proliferation. [score:5]
Above results have shown that forced -expression of miR-135b-5p silenced Ppm1e and inhibited osteoblastoma cell proliferation. [score:5]
Yet, unlike control cells (See Figure 3), forced -expression of miR-135b-5p failed to further inhibit the proliferation of Ppm1e-silneced cells (Figure 4G). [score:5]
As shown in Figure 5A, AMPKα1 shRNA knockdown or T172A mutation almost completely blocked AMPK activation (p-AMPKα1 at Thr-172) in vec-miR-135b -expressing cells. [score:5]
Tumor growth curve results in Figure 6A demonstrated that growth of U2OS tumors was largely inhibited after expressing Ppm1e shRNA or Vec-miR-135b. [score:5]
U2OS tumor growth in SCID mice is inhibited after expressing Ppm1e shRNA or miR-135b-5p. [score:5]
Remarkably, forced -expression of miR-135b-5p failed to further inhibit the proliferation of Ppm1e-silneced cells. [score:5]
These results demonstrate that forced miR-135b-5p expression inhibits osteoblastoma cell proliferation. [score:5]
In the current study, we showed that miR-135b-5p expression silences Ppm1e, which activates AMPK to inhibit osteoblastoma cell proliferation. [score:5]
These results together imply that Ppm1e is the direct and primary target of miR-135b-5p in mediating its actions in osteoblastoma cells. [score:4]
In order to block AMPK activation, AMPKα1 shRNA [20, 27] or a dominant negative mutation of AMPKα1 (T172A, Flag-tagged) [20, 27] was introduced to vec-miR-135b -expressing MG-63 cells (“L1”, see Figure 2). [score:4]
shRNA -mediated knockdown of Ppm1e mimicked miR-135b-5p's actions, and similarly induced AMPK activation and inhibited osteoblastoma cell proliferation. [score:4]
Expressions of miR-135b-5p and Ppm1e were examined. [score:3]
AMPKα1 shRNA knockdown or mutation abolishes miR-135b-5p's actions against osteoblastoma cells. [score:3]
Expression of miR-135b-5p, as expected, was unchanged in Ppm1e-silenced cells (Figure 4C). [score:3]
Recent studies have identified a Ppm1e -targeting miRNA: miR-135b-5p [19, 20]. [score:3]
Above results confirmed significant AMPK activation in miR-135b-expressed cells. [score:3]
Forced -expression of miR-135b. [score:3]
As shown in Figure 4F, the level of miR-135b-5p was again elevated after expression of vector. [score:3]
Estimated daily tumor growth (in mm [3] per day) was also significantly lower in Ppm1e shRNA- or Vec-miR-135b -expressing tumors (Figure 6B). [score:3]
As demonstrated, Ppm1e mRNA was indeed depleted in Ppm1e shRNA- or Vec-miR-135b -expressing tumors (Figure 6E). [score:3]
These results suggest that activation of AMPK is required for miR-135b-5p -induced MG-63 cell proliferation inhibition. [score:3]
Thus, we therefore exogenously expressed miR-135b vector in the two MG-63 lines with Ppm1e shRNA (“shPpm1e-1” and “shPpm1e-1”). [score:3]
Stable MG-63 cells with miR-135b vector (“Vec-miR-135b”, “L1”) or the empty vector (“Vec”, pSuper-puro) were further constructed with AMPKα1 shRNA (“shAMPKα1”), scramble control shRNA (“sh-C”) or a dominant negative mutation of AMPKα1 (T172A, Flag-tagged, ““dnAMPKα1”), expressions of listed proteins were shown (A); miR-135b-5p mRNA expression was tested by qRT-PCR assay (B); Cell proliferation was tested by the CCK-8 assay (C) and BrdU ELISA assay (D). [score:3]
Further, forced -expression of miR-135b-5p in MG-63 cells also dramatically decreased the number of colonies (Figure 3B). [score:3]
In cultured human osteoblastoma cells (MG-63 and U2OS lines), forced -expression of miR-135b depleted Ppm1e, leading to profound AMPK activation (AMPKα1 phosphorylation at Thr-172). [score:3]
In the three lines (“L1/L2/L3”) of miR-135b-5p -expressing U2OS cells, CCK-8 OD (Figure 3D), colony formation (Figure 3E) and BrdU incorporation ELISA OD (Figure 3F) were all decreased. [score:3]
Next, a miR-135b expression vector (“Vec-miR-135b”, a gift from Dr. [score:3]
Figure 5Stable MG-63 cells with miR-135b vector (“Vec-miR-135b”, “L1”) or the empty vector (“Vec”, pSuper-puro) were further constructed with AMPKα1 shRNA (“shAMPKα1”), scramble control shRNA (“sh-C”) or a dominant negative mutation of AMPKα1 (T172A, Flag-tagged, ““dnAMPKα1”), expressions of listed proteins were shown (A); miR-135b-5p mRNA expression was tested by qRT-PCR assay (B); Cell proliferation was tested by the CCK-8 assay (C) and BrdU ELISA assay (D). [score:3]
Ppm1e expression (Figure 5A) and miR-135b-5p level (Figure 5B) were unchanged in AMPKα1-silenced or -mutant cells. [score:3]
BrdU ELISA OD in these miR-135b-5p -expressing cells was also decreased (Figure 3C). [score:3]
The scramble shRNA control (“sh-C”) didn't change Ppm1e expression, miR-135b-5p level, AMPK activation and MG-63 cell proliferation (Figure 4A–4E). [score:3]
U2OS cells, stably expressing Ppm1e shRNA (“-1”, see Figure 4), Vec-miR-135b (“L1”, see Figure 2) or empty vector (“Vec”, see Figure 2), were inoculated into the severe combined immunodeficient (SCID) mice via s. c. injection. [score:3]
Importantly, AMPKα1 shRNA knockdown or dominant negative mutation almost abolished miR-135b-5p -induced actions in osteoblastoma cells. [score:3]
Once again, forced -expression of miR-135b-5p in three U2OS cell lines (“L1/L2/L3”) (Figure 2D) led to Ppm1e depletion (Figure 2E and 2F) and significant AMPK activation (Figure 2F). [score:3]
Introduction of the non-sense microRNA control (“mi-C”) showed no effect on expressions of miR-135b, Ppm1e and p-AMPKα1 (Figure 2A–2F). [score:3]
We conclude that miR-135b silences Ppm1e to provoke AMPK activation and inhibit osteoblastoma cell proliferation. [score:3]
Via selection by puromycin, a total of three stable MG-63 cell lines (“L1/L2/L3”) expressing Vec-miR-135b were established. [score:3]
Collectively, miR-135b-5p expression causes Ppm1e silence and AMPK activation in human osteoblastoma cells. [score:3]
The expression of mature miR-135b was tested by the TaqMan microRNA assay as described [47]. [score:2]
miR-135b-5p expression in the resulting stable cells was tested by qRT-PCR assay. [score:2]
Figure 4Stable MG-63 cells with listed Ppm1e shRNA (“shPpm1e-1” or “shPpm1e-1”) or scramble shRNA control (“sh-C”), as well as the parental control MG-63 cells (“Ctrl”) were subjected to qRT-PCR assay to test expression of Ppm1e mRNA (A) and miR-135b-5p (C); Listed proteins in above cells were also tested, and blot data were quantified (B). [score:2]
MG-63 cells with listed Ppm1e shRNA (“shPpm1e-1” or “shPpm1e-1”) were also transfected with miR-135b vector (“Vec-miR-135b”), expression of miR-135b-5p was tested afterwards (F); Cell proliferation was examined by CCK-8 assay (G). [score:2]
Stable MG-63 cells with listed Ppm1e shRNA (“shPpm1e-1” or “shPpm1e-1”) or scramble shRNA control (“sh-C”), as well as the parental control MG-63 cells (“Ctrl”) were subjected to qRT-PCR assay to test expression of Ppm1e mRNA (A) and miR-135b-5p (C); Listed proteins in above cells were also tested, and blot data were quantified (B). [score:2]
The potential effect of miR-135b-5p on osteoblastoma cell growth in vivo was tested. [score:1]
Therefore, further studies will be needed to explore the downstream signalings of AMPK that mediate miR-135b's actions in osteoblastoma cells. [score:1]
Remarkably, we imply that AMPK activation could be responsible for miR-135b-5p -mediated anti-osteoblastoma cell activity. [score:1]
Cell Counting Kit-8 (CCK-8) cell proliferation assay results in Figure 3A clearly showed that proliferation of MG-63 cells with miR-135b vector (three lines, “L1/L2/L3”, see Figure 2) was significantly inhibited, as compared to cells with non-sense microRNA control (“mi-C”) or empty vector (Figure 3A). [score:1]
Three million of U2OS cells (per mouse), with Ppm1e shRNA or “Vec-miR-135b”, were inoculated subcutaneously (s. c. ) into the flanks of the mice. [score:1]
The miR-135b pSuper-puro-GFP vector (“Vec-miR-135b”) and miR-control (“miR-C”) vector were provided by Dr. [score:1]
On the other hand, miR-135b-3p level in above cells was quite low (Data not shown). [score:1]
Expressions of miR-135b-5p (A, qRT-PCR assay), Ppm1e mRNA (B, qRT-PCR assay) and listed proteins (C–D,) in ten (10) different human osteoblastoma tissues (“Tumor”) and surrounding normal bone tissues (“Normal”) were tested. [score:1]
Stable U2OS cells, with Ppm1e shRNA (“-1”), Vec-miR-135b (“L1”) or empty vector (“Vec”), were inoculated into the SCID mice via s. c. injection. [score:1]
These results imply that miR-135b-5p could possibly be a novel anti-cancer microRNA (“anti-oncomir”) in osteoblastoma. [score:1]
Figure 6Stable U2OS cells, with Ppm1e shRNA (“-1”), Vec-miR-135b (“L1”) or empty vector (“Vec”), were inoculated into the SCID mice via s. c. injection. [score:1]
Figure 1Expressions of miR-135b-5p (A, qRT-PCR assay), Ppm1e mRNA (B, qRT-PCR assay) and listed proteins (C–D,) in ten (10) different human osteoblastoma tissues (“Tumor”) and surrounding normal bone tissues (“Normal”) were tested. [score:1]
At the end of the experiments (Week-7), the weight of tumors with Ppm1e shRNA or Vec-miR-135b was also much lower than “Vec” control tumors (Figure 6C). [score:1]
Based on the results above, we speculated that miR-135b-5p could possibly be invalid in Ppm1e -depleted cells. [score:1]
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3
[+] score: 225
For example, the targets of the mir-135 family, a family that was up-regulated in the vestibule, were enriched in a set of proteins down-regulated in this tissue; and the targets of mir-205, a miRNA that exhibited a higher expression in the cochlea, were depleted in a set of proteins also up-regulated in the cochlea. [score:16]
We noted that targets of mir-135 were marginally enriched in the set of all proteins up-regulated in the cochlea (P = 0.075), and a statistically significant enrichment was found only when considering genes up-regulated in the cochlea only on the protein level (i. e., genes without significant mRNA changes between the two tissues, P = 0.047). [score:9]
Thus, for six miRNA families – mir-135, mir-205, mir-142-3p, mir-15/16, mir-218 and mir-24 - we obtained evidence for their functional relevance in the inner ear on two levels: (a) the miRNAs were differentially expressed between the two tissues; and (b) their predicted targets were differentially expressed in a manner consistent with the currently accepted mo del of miRNA regulation. [score:8]
miR-135b regulates PSIP1-P75 expression by inhibition of translation. [score:8]
miR-135b down-regulates PSIP1-P75 (red) expression in the vestibular hair cells while its expression remains relatively high in the cochlear hair cells. [score:8]
miR-135b was up-regulated 4-fold in the vestibule and miR-124a was up-regulated 8-fold in the cochlea (Figure 1C). [score:7]
analysis revealed a reduction in miR-135b expression and similar Psip1 mRNA expression level in both the cells transfected with the shRNA targeting miR-135b and transfected with the anti-miR negative control (Figure 4D; n = 3, P = 0.66; Student's t-test). [score:7]
The most notable miRNA for which we identified translationally repressed targets was miR-135b, the miRNA with the highest differential expression in our dataset. [score:7]
The miRNAs with the greatest differential expression were miR-135b (expressed 2.5 times higher in the vestibule) and miR-124a (expressed 4 times higher in the cochlea). [score:7]
These results indicate that miR-135b down-regulates the expression of PSIP1-P75 protein but does not affect the mRNA levels. [score:6]
miR-135b down-regulates PSIP1-P75 protein expression. [score:6]
Transient co -expression of this vector with a miR-135b expressing vector revealed that miR-135b reduced luciferase expression levels by approximately 40% (Figure 4E; as compared to a mutated Luc- Psip1-P75-3′UTR control. [score:6]
The overall effect of miR-135b in the inner ear is summarized in Figure 5. In this scheme, we propose a unique mechanism by which miR-135b down-regulates PSIP1-P75 expression in the vestibular hair cells, whereas it remains relatively high in the cochlea. [score:6]
For further study, we selected miR-135b and miR-205, for which miRNA target enrichment or depletion, respectively, were detected only at the protein expression level and therefore would not have been identified by analyzing transcript data alone. [score:5]
We chose to focus on miR-135b due to its intriguing cell specific expression pattern and its high differential expression between the vestibule and cochlea. [score:5]
miR-135b (blue) is expressed in the vestibular hair cells, whereas no expression is detected in the cochlear hair cells. [score:5]
shRNA targeting miR-135b (X-miR-135b, oligoengine) or an anti-miR negative control were transfected to Cal51 cells that naturally express miR-135b. [score:5]
The P52 isoform of PSIP1 does not have a target site within its 3′UTR and is therefore not a potential target of miR-135b. [score:5]
0018195.g005 Figure 5 miR-135b (blue) is expressed in the vestibular hair cells, whereas no expression is detected in the cochlear hair cells. [score:5]
miR-135b and miR-124a, the miRNAs with the highest differential expression in the array, exhibited significant differential expression between the cochlear and vestibular sensory epithelia in the validation (4-fold and 8-fold, respectively). [score:5]
Cal51 cells were transfected with either a plasmid expressing shRNA targeting miR-135b or an anti-miR negative control. [score:5]
Semi-quantitative western blot analysis exhibited a 10-fold increase in PSIP1-P75 protein abundance in the cells expressing shRNA targeting miR-135b (Figure 4E; as compared to transfection with an anti-miR negative control. [score:4]
Furthermore, our data predict that miR-135b regulates three targets in the vestibule, PSIP1-P75 (also called LEDGF) and PC4, two interacting transcriptional coactivators [25], [26] and ARCN1, a subunit of the coat protein I (COPI) complex required for intracellular trafficking [27]. [score:4]
Furthermore, we demonstrated the translational regulation of PC4 and SFRS1 interacting protein 1 (PSIP1), a transcriptional coactivator previously unknown to function in the inner ear, by miR-135b. [score:4]
The distinct expression pattern of miR-135b most probably points to a specific regulation mechanism that exists in the vestibular hair cells but not in the cochlear hair cells. [score:4]
Significantly, the identification of a bona-fide miRNA-target pair, miR-135b and PSIP1-P75, predicts a role for this pair in inner ear cell survival, protection against stress, differentiation, cell fate determination and development, and may explain differences in regeneration of vestibular vs. [score:4]
Each of the targets contains a single sequence complementary to the miR-135b seed within their 3′ UTR. [score:3]
Interestingly, the efficiency by which miR-135b silences PSIP1-P75, as identified by our in vitro analysis, is much higher than previously expected for targets with only a single binding site for a miRNA seed [2]. [score:3]
Expression patterns for miR-135b (C) and miR-205 (D) were consistent with the miRNA array analysis. [score:3]
Briefly, MCF-7 cells were grown in 24-well plates and transfected using JetPEI reagent (Polyplus transfection™) with either 5 ng of Luc- Psip1-P75-3′UTR or a mutated control, 5 ng Renilla and 0.5 µg of miR-135b (miRNA expression vector obtained as a gift from Reuven Agami, [61]). [score:3]
Of the two, only P75 contains a sequence within its 3′ UTR with the potential of being targeted by miR-135b. [score:3]
Consistent with the miRNA microarray results, miR-135b exhibited specific expression in vestibular organs hair cells. [score:3]
In situ hybridization demonstrated specific expression of miR-135b in vestibular hair cells. [score:3]
The spatial expression pattern of miR-135b and miR-205 in the inner ear of P0 mice was determined using in situ hybridization (ISH; Figure 3), and suggested differences in miRNA function across the cochlea and vestibular organs. [score:3]
Of the three putative targets of miR-135b, we chose to further validate the interaction with the P75 isoform of PSIP1. [score:3]
For miR-135b inhibitor treatment, Cal51 cells were transfected using JetPEI reagent (Polyplus transfection™) with a pSUPER-GFP plasmid encoding either shRNAs against mouse miR-135b or negative control shRNA (Oligoengine). [score:3]
Therefore, it is likely that miR-135b is transcribed as part of Lemd1, leading to a similar expression pattern. [score:3]
Cal51, breast carcinoma, cells were found to express high levels of miR-135b, and relatively low levels of PSIP1-P75. [score:3]
For two miRNAs, miR-135b and miR-205, we localized their cell specific expression in the inner ear using in situ hybridization. [score:3]
Unlike miR-135b, these miRNAs are expressed both in the cochlear and vestibular hair cells. [score:3]
To better understand miR-135b function in the inner ear, we studied its spatial expression. [score:3]
Distinct spatial expression patterns of miR-135b and miR-205 in the newborn mouse inner ear. [score:3]
For miR-135b regulation analysis in shRNA transfected Cal51 cells, transfected cells were lysed and frozen at -80°C. [score:2]
Taken together, our results demonstrate the regulation of PSIP1-P75 by miR-135b in vestibular hair cells. [score:2]
By this means, miR-135b might serve as a cellular effector, involved in regulating the differences between the cochlear and vestibular hair cells and thus contributes to their distinct cell identities and maintaining their specific functions. [score:2]
We hypothesize that PSIP1-P75 and miR-135b might play a role in regulating these processes in the cochlear hair cells, whereas in vestibular hair cells they are modulated by other miRNA. [score:2]
For miR-135b regulation analysis in shRNA transfected Cal51 cells, transfected cells were spun-down and frozen at -80°C. [score:2]
Due to the similarity between miR-135b and miR-135a, we predict that miR-135a also regulates PSIP1-P75 in the vestibular system. [score:2]
miR-135b is located within the first intron of the LEM domain containing 1 (Lemd1) gene. [score:1]
In addition, miR-135b was detected in the neurons of the vestibular and spiral ganglia. [score:1]
Schematic representation of a possible role of miR-135b in the inner ear. [score:1]
In vitro analysis further proved an interaction between miR-135b and PSIP1-P75. [score:1]
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4
[+] score: 76
Among these, the expression of only 2 miRNAs (miR-135b and miR-155) was markedly increased in the infected group (Fold-regulation value >3), whereas the expression of 5 miRNAs (miR-206, miR -802, miR-122, miR-377, miR-33) was decreased (Fold-regulation value <3; Table S1). [score:7]
org) revealed that 4 of the 5 miRNAs up-regulated in our mo del, namely miR-135b, miR-142a, miR-150, and miR155, have potential binding sites within the 3′ UTR of the mRNA of the pro-apoptotic gene TP53INP1 and hence would be able to down-regulate it. [score:7]
Upregulation of miR135b was never described before in GML cases and neither was the upregulation of miR-142a in mice sera. [score:7]
Hence, miR-135b, miR-142a, miR-150, and miR155 seem to down-regulate TP53INP1 production via mRNA translational repression but not by mRNA degradation (Figures 2, 4). [score:6]
miR-21a, miR-135b et miR-155 indirectly target the PI3K/AKT signaling pathway: indeed, miR-21a and miR-155 activate the PI3K/AKT signaling pathway by targeting PTEN and SHIP-1 respectively, and promote cell survival (Thorns et al., 2012; Sheedy, 2015; Lu et al., 2017). [score:6]
As previously mentioned, cell survival may also be mediated by inhibition of TP53INP1 translation by miR-135b, miR-142a, miR-150, and miR-155. [score:5]
In conclusion, five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) are up-regulated in gastric lymphomagenesis in mice, were identified in our study. [score:4]
On the contrary, miR-135b down-regulates JAK2 involved in the activation of this pathway (Lawrie, 2012). [score:4]
The final list was: miR-21, miR-135b, and miR-155 [with fold-regulation values > 3 (Table 1)] as well as miR-142a and miR-150 as their over -expression at the lymphoma stage was described by others (Saito et al., 2012; Thorns et al., 2012; Gebauer et al., 2014; Fernandez et al., 2017). [score:4]
Figure 1Relative expression levels of miR-21a, miR-135b, miR-142a, miR150, and miR-155 in Helicobacter pylori infected and non-infected (NI) NTx and d3Tx mice stomachs. [score:3]
Relative expression levels of miR-21a, miR-135b, miR-142a, miR150, and miR-155 in NTx and d3Tx mice. [score:3]
A single miRNA can act both as an oncogene (miR-21a, miR-135b, miR-142a, miR-150, and miR-155) or a tumor suppressor (miR-135b, miR-150), thus making the mechanisms involved in lymphomagenesis more complex. [score:3]
By using the unique material obtained from a previous study (Chrisment et al., 2014), in which we were able to induce GML in H. pylori-infected d3Tx mice, we showed an over -expression of miR-21a, miR-135b, miR-142a, miR-150, and miR-155 in mice stomachs at the lymphoma stage. [score:3]
Using the material obtained in Chrisment et al. (2014), a set of 5 miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) was identified as being over-expressed in the stomachs of the GML-developing d3Tx mice. [score:3]
The expression of miR-135b is increased in various cancers such as colorectal cancers and acts as an oncomir (Valeri et al., 2014), but it has never been studied in GML. [score:3]
Our results suggest that this transcript can be targeted also by two other miRNAs, i. e., miR-135b and miR-150. [score:3]
Over -expression of miR-21a, miR-135b, miR-142a, miR-150, and miR-155 was confirmed at the GML stage (Figure 1) compared to d3Tx and to NTx mice (NI and infected). [score:2]
miR-135b, miR-142a, miR-150, and miR155 are potentially able to bind to the 3′ UTR region of the Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) mRNA. [score:1]
In order to confirm the results of the, the expression of miR-21a, miR-135b, miR-142a, miR-150, miR-155 in d3Tx, and NTx mice stomachs was individually performed by RT-qPCR, using the miScript Universal Primer and specific primers for each miRNA (Qiagen) at a final concentration of 0.25 μM and the SYBR® Green Premix Ex Taq™ (Tli RNaseH Plus; Takara, Saint-Germain-en-Laye, France) for qPCR of each miRNA-RT sample. [score:1]
Relative expression of miR-21a, miR-135b, miR-142a, miR-150, and miR-155 was therefore evaluated in NI and infected d3Tx mice sera by RT-qPCR. [score:1]
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5
[+] score: 64
Other miRNAs from this paper: mmu-mir-429
Based on these results, we propose that ThIIA up-regulates miR-135b to downregulate Ppm1e, which possibly leads to AMPKα1 phosphorylation and AMPK activation, thus protecting neuronal cells from OGDR. [score:7]
In the current study, we demonstrated that ThIIA upregulated miR-135b and downregulated the AMPK phosphatase Ppm1e, which possibly led to AMPKα1 phosphorylation and AMPK activation. [score:7]
Indeed, knockdown of Ppm1e by targeted shRNA or forced expression of miR-135b also activated AMPK signaling and protected SH-SY5Y cells from OGDR, mimicking ThIIA functions. [score:6]
As shown in Figure 6D, forced expression of miR-135b-Vec or the Ppm1e shRNA caused dramatic downregulation of Ppm1e mRNA in SH-SY5Y cells. [score:6]
For instance, Cui's group demonstrated that miR-135b expression downregulated Ppm1e to activate AMPK signaling and protected osteoblastic cells [47]. [score:6]
It should be noted that Ppm1e mRNA and protein expression as well as miR-135b expression were not changed by OGDR in SH-SY5Y cells (Figure 6A–6C). [score:5]
ThIIA increases miR-135b buts downregulates Ppm1e in neuronal cells. [score:4]
microRNA-135b expression. [score:3]
Next, a miR-135b expressing construct (“miR135b-Vec”, a gift from Dr. [score:3]
Ppm1e protein expression was almost completed depleted in stable cells with miR135b-Vec or the shRNA (Figure 6E). [score:3]
On the other hand, the Ppm1e -targeting mRNA, miR-135b, was increased by ThIIA (Figure 6C). [score:3]
The lentiviral microRNA-135b (miR-135b) expression vector (0.15 μg construct per transfection), provided by Dr. [score:3]
Expression of miRNA-135b-5p in above cells was verified using qRT-PCR assay. [score:2]
qRT-PCR assay results in Figure 6F confirmed increased miR-135b expression in cells with the miR135b-Vec, which was not changed by Ppm1e shRNA (Figure 6F). [score:2]
miR-135b -mediated silence of Ppm1e could be the key mechanism of AMPK activation by ThIIA. [score:1]
Therefore, activation of AMPK by miR-135b or Ppm1e shRNA also protected SH-SY5Y cells from OGDR (Figure 6G and 6H). [score:1]
Notably, miR-135b and Ppm1e shRNA both caused profound AMPK activation, which was evidenced by increased phosphorylations of AMPKα1 (Thr-172) and ACC (Ser-79) (Figure 6E). [score:1]
Significantly, SH-SY5Y cells with miR-135b-Vec or the Ppm1e shRNA were largely protected from OGDR, presenting with decreased viability reduction (Figure 6G) and reduced LDH release following OGDR (Figure 6H). [score:1]
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6
[+] score: 48
Predicted targets for miR-135b (TargetScan or Pictar) that were differentially expressed (downregulated) included the following: checkpoint suppressor1,runt related transcription factor 2 (runx2), and phosphodiesterase 8b. [score:12]
As such, we searched for mRNA targets of miR-135b and miR-449a using the target-prediction softwares TargetScan and Pictar. [score:7]
Runx2 and lef1 are the downstream targets of WNT signaling suggesting that miR-135b and miR-449a may have a common function in regulating WNT signaling. [score:4]
We hypothesize that some of the genes, including the Saa family and chemokines, are the direct targets of miR-135b and that miR-135b could be acting to resolve the inflammation process. [score:4]
Real time RT-PCR analysis confirmed the upregulation of miR-449a, miR-1, and miR-135b (Fig. 1B). [score:4]
For example, differential expression of miR-135b is found in human colon cancer samples [Sarver et al., 2009] and miR-449a is associated with antitumor activity in prostate cancer cells [Noonan et al., 2009]. [score:3]
However, it appears that the effect of the observed 6- and 60-fold induction of miR-449a and miR-135b on transcript levels of their predicted targets is negligible. [score:3]
First, the genes targeted by miR-449a and miR-135b in response to particle exposure may be different than the ones predicted in silico. [score:3]
gr/tarbase/) did not reveal any known targets of miR-449a or miR-135b. [score:3]
Analysis by qRT-PCR confirmed the higher levels of miR-449a (fold six), miR-1 (2.6-fold), and miR-135b (60-fold) in this study (Fig. 1B) but not the suppression of miR-223 and miR-92a. [score:3]
We have recently confirmed induction of miR-135b in other inflammatory mo dels including particle -induced inflammation (Halappanavar et al., unpublished data). [score:1]
Thus, miR-1, miR-135b, and miR-449a may play a role in these biological processes. [score:1]
[1 to 20 of 12 sentences]
7
[+] score: 43
Of these, 12 (mir-9, mir-200c, mir-708, mir-377, mir-26b, mir-296, mir-369, mir-32, mir-1965, mir-1190, mir-135b and mir-201) were differentially up-regulated and five (mir-291a, mir-190b, mir-297c, mir-713 and mir-470) were differentially down-regulated. [score:7]
Among them, miR-135b and miR-708 displayed a significant up-regulation in primary hippocampal neurons with H [2]O [2] stimulation for 6 h. The regulation of miRNA on its target genes is a rapid process, and the oxidative stress plays an important role in the onset of neurodegenerative disorders. [score:7]
In addition, PRP19beta, another miR-135 target gene, was founded to inhibit neurons differentiation and stimulate glial cells growth [35]. [score:5]
Recently, one study confirmed that Siah, a predicted target of the miR-135 family, regulated neuronal migration, development of nervous system and morphogenesis of the brain by inducing Pard3A protein ubiquitination [34]. [score:5]
We found that the level of miR-135b was significantly upregulated in the primary hippocampal neurons by H [2]O [2] treatment. [score:4]
To further illuminate the possible roles of miR-135b and miR-708 in the pathogenesis of AD, Gene Ontology (GO) enrichment for biological processes and molecular functions of miR-135 and miR-708 targets were performed. [score:3]
Functional Analysis of Targets of miR-135b and miR-708. [score:3]
Based on the relevance to neurodegenerative disorders, their expression levels (total counts in hippocampus) and the possible functions predicted by KEGG considered [25], we chose five miRNAs, including miR-32, miR-196b, miR-26b, miR-708 and miR-135b, to validate microarray results among 17 miRNAs. [score:2]
Taken together, it can be predicted that miR-135b-participated hippocampal neuron impairment is regulated, at least in part, via decreasing hippocampal Siah and PRP19beta levels. [score:2]
It was showed that miR-135b (p < 0.01) and miR-708 (p < 0.05) expressed at higher levels in H [2]O [2] -treated primary hippocampal neurons compared with control cells, consistent with the results of microarray (Figure 4). [score:2]
It is reported that miR-135b, one important member of the miR-135 family, played essential roles in development of many tumors, such as anaplastic large cell lymphoma [31], osteosarcoma [32] and colon cancer [33]. [score:2]
The results revealed that miR-135 was related to DNA recombination, protein ubiquitination, protein amino acid autophosphorylation and transcription factor binding (Table 2). [score:1]
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8
[+] score: 34
Moreover, miR-135b suppressed the T-helper (Th) 2 master regulators STAT6 and GATA3, and inhibition of miR-135b suppressed the production of a Th17 pro-inflammatory cytokine, IL-17, by NPM/ALK cells. [score:8]
When analyzing the differences of miRNA regulation in ALK(+) versus ALK(−) cells following inactivation of STAT3 by shRNA -mediated ALK or STAT3 knockdown, miR-135b expression was most prominently altered, with a significant upregulation in ALK(+) ALCL cell lines and human primary ALK(+) ALCL samples compared to ALK(−) ALCL cells [30, 43]. [score:7]
MiR-135b targets the FOXO1 transcription factor in ALK(+) ALCL cell lines, which is critical as FOXO1 can promote the expression of the cell cycle inhibitors p21 and p27. [score:6]
Compared to ALK(−) ALCLs, miR-203, miR-135b, miR-886-5p/3p, miR-20b, miR-106a and miR-183 were significantly upregulated in ALK(+) ALCLs while others (miR-155, miR-181a, miR-210, miR-29a/b, miR-342-5p/3p, miR-369-3p miR-374a/b, miR-423-5p, miR-625, miR-205, miR-146a and miR-26a) were down-regulated (Table 1). [score:6]
This indicates that miR-135b -mediated Th2 suppression may lead to the ALCL immunophenotype overlapping with Th17 cells [30]. [score:3]
In accordance with the pro-angiogenic function of IL-17, miR-135b inhibition also reduced tumor angiogenesis and growth in vivo (Table 3). [score:3]
2.2.2. miR-135b. [score:1]
[1 to 20 of 7 sentences]
9
[+] score: 27
[21] Out of the nine miRNAs that were screened, four were upregulated (miR-135b, miR-155, miR-205 and miR-206: Figure 1a) and five were downregulated (miR-31, miR-148a, miR-181c, miR-200b and miR-210: Figure 1b). [score:7]
[21]Out of the nine miRNAs that were screened, four were upregulated (miR-135b, miR-155, miR-205 and miR-206: Figure 1a) and five were downregulated (miR-31, miR-148a, miR-181c, miR-200b and miR-210: Figure 1b). [score:7]
Overexpression of miR-155, miR-205 and miR-206 resulted in a complete loss of HC11 dome formation, whereas, overexpression of miR-135b resulted in an increase in HC11 dome formation (Supplementary Figures 1a and b). [score:5]
For example, it is possible that repression of Brca1 in the epithelial compartment of the mammary gland causes upregulation of miR-135b, miR-155 and miR-205 in nonepithelial cells of the mammary gland. [score:4]
In contrast to the analysis of Brca1 -deficient mammary glands (Figure 1a), upregulation of miR-135b, miR-155 and miR-205 was not observed in HC11 cells in which Brca1 levels have been repressed using siRNA (Figure 1c). [score:4]
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10
[+] score: 26
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-18a, hsa-mir-21, hsa-mir-27a, hsa-mir-96, hsa-mir-99a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30b, mmu-mir-99a, mmu-mir-124-3, mmu-mir-125b-2, mmu-mir-9-2, mmu-mir-135a-1, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, hsa-mir-181a-2, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-181a-1, hsa-mir-200b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, mmu-mir-200a, 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-18a, mmu-mir-21a, mmu-mir-27a, mmu-mir-96, mmu-mir-181a-1, mmu-mir-199a-2, mmu-mir-135a-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, hsa-mir-200a, hsa-mir-135b, dre-mir-182, dre-mir-183, dre-mir-181a-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-15a-1, dre-mir-15a-2, dre-mir-18a, dre-mir-21-1, dre-mir-21-2, dre-mir-27a, dre-mir-27b, dre-mir-27c, dre-mir-27d, dre-mir-27e, dre-mir-30b, dre-mir-96, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-125b-1, dre-mir-125b-2, dre-mir-125b-3, dre-mir-135c-1, dre-mir-135c-2, dre-mir-200a, dre-mir-200b, dre-let-7j, dre-mir-135b, dre-mir-181a-2, dre-mir-135a, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-let-7k, dre-mir-181a-4, dre-mir-181a-3, dre-mir-181a-5, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
In this study, miR-135b was found in LNA arrays to be up-regulated in the vestibule, while its targets were enriched in a protein dataset and down-regulated in the vestibule. [score:9]
An example of such a miR-target pair is miR-135 and Psip, PC4- and SF-2 interacting protein/Ledgf (Elkan-Miller et al, 2011), which has been implicated in transcriptional regulation of stress-related genes, having an anti-apoptotic effect, involved in mRNA splicing, cell survival and is part of a fusion gene in leukaemia. [score:4]
The analysis predicted PSIP1-P75 as one of potential targets of miR-135b. [score:3]
miR-135 is reduced in the cochlear hair cells, while its expression is high in vestibular hair cells. [score:3]
This mo del suggests that miR-135b regulation of Psip1 plays a role in hair cell development and survival. [score:3]
In situ hybridization confirmed the differential expression of miR-135b in vestibular hair cells as compared to cochlear hair cells at P0. [score:2]
The pathways shown demonstrate potential inner ear functional pathways implicated in the miR135b-Psip regulatory network. [score:2]
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11
[+] score: 21
Halappanavar, S. et al. IL-1 Receptor Regulates microRNA-135b Expression in a Negative Feedback Mechanism during Cigarette Smoke-Induced Inflammation. [score:4]
Interestingly, miR-135b and miR-155 were significantly up-regulated, both in COPD patients (Adj. [score:4]
Figure 5Spearman correlation analyses between the expression of (a) miR-135b and % dendritic cells (DCs) in lung following 4 weeks of air or CS exposure. [score:3]
In agreement with our data, an increase in miR-135b-5p expression was already demonstrated in lungs of mice that were exposed to CS for 4 days and for 18 months, besides the observation that miR-135b-5p is also highly inducible upon challenge of the airways with other noxious particles 22– 24. [score:3]
By focusing on the overlap between subacute and chronic CS exposure within the same compartment, or the overlap between miRNAs with altered expression levels in BAL and lung, we narrowed the pool of interesting miRNAs down to 18: let-7b, let-7c, miR-135b, miR-138, miR-146a, miR-148a, miR-152, miR-155, miR-21, miR-26a, miR-30a-5p, miR-30c, miR-31, miR-31*, miR-322*, miR-342-3p, miR-376b* and miR-449. [score:3]
On top of the list, miR-135b displayed the highest fold change in lung tissue (Fold change = 13.59, Table  2). [score:1]
p-value (miR-135b and miR-155) = 0.004) (Fig.   6a) (Table  S2). [score:1]
p-value (miR-135b) = 0.017; Adj. [score:1]
After subacute CS exposure, miR-135b correlated strongly with percentage DCs (adj. [score:1]
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[+] score: 20
We focused on the 4 miRNAs that were differentially expressed in early stage lesions of both genetic and inflammatory origin (miR-215, miR-31, miR-708, miR-135b). [score:3]
Eight high priority miRNAs were identified: miR-215, miR-137, miR-708, miR-31, and miR-135b were differentially expressed in APC tumors and miR-215, miR-133a, miR-467d, miR-218, miR-708, miR-31, and miR-135b in colitis -associated tumors. [score:3]
Nevertheless, there is evidence that miR-31 [12]– [17],, miR-135b [13]– [15], [20], [21], [33], and miR-215 [18], [21]– [23], [37] are differentially expressed in fully transformed colonic epithelial cells. [score:3]
A literature survey indicates that some of these focus miRNAs have been previously reported to be differentially expressed in primary human colon cancers, as shown in Table 2. MicroRNAs miR-31 and miR-135b have been reported to be induced in colon cancer, similar to the response that we have observed in early stage tumors in chronically inflamed or APC [Min/+] mice. [score:3]
Four of these (miR-215, miR-708, miR-31, and miR-135b) were common to both tumors types, and dysregulation of these miRNAs was confirmed in an independent sample set. [score:2]
This curation step reduced the number of high probability differentially expressed miRNAs in APC tumors to 5 and the number of such miRNAs in CAC tumors to 7. As shown in Table 1, two miRNAs were repressed in APC tumors (miR-215 and miR-137), compared to adjacent control epithelium, whereas 3 miRNAs were induced (miR-708, miR-31, miR-135b). [score:2]
As shown in Figure 4, repression of miR-215 was confirmed in both CAC and APC tumor samples, whereas induction of miR-708, miR-31, and miR-135b was likewise confirmed in tumors of both origins. [score:1]
Three miRNAs were induced in both APC and CAC samples (miR-31, miR-135b, and miR-708) and 1 miRNA was repressed in both APC and CAC samples (miR-215). [score:1]
Nevertheless, we were able to validate our four most prominent miRNAs (miR-215, miR-708, miR-135b, miR-31) in an independent set of APC and CAC tumors. [score:1]
Summary of top GO functions identified for miR-215, miR-31, miR-135b, and miR-708 by Ingenuity Pathway Analysis. [score:1]
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13
[+] score: 20
We also examined miR-135b expression, which was significantly upregulated by chronic exposure to cigarette smoke, with their being an approximately 20-fold increase in expression. [score:8]
There was a dramatic upregulation of miR-135b and a more modest change in miR-146a whereas miR-96 was only increased in cigarette smoke-exposed Ahr [−/−] mice. [score:4]
miRNA expression was assessed by two-step TaqMan [®] RT-PCR (Applied Biosystems, Carlsbad, CA) for miR-196, miR-146a, miR-135b, miR-96, miR-34c, and U6 snRNA, a small nuclear RNA (snRNA) used as an internal control for miRNA analysis. [score:3]
Recently, Halappanavar and colleagues demonstrated that miR-135b is significantly increased in the lungs of smoke-exposed mice as a mechanism to resolve the inflammatory response 49, supporting an anti-inflammatory role for miR-135b. [score:1]
The miRNA with the largest fold-change was miR-135b (approximately 71-fold in Ahr [+/−] mice) (Fig. 5). [score:1]
Therefore, we next selected miR-146a and miR-135b in conjunction with miRNA exhibiting large relative differences between Ahr [−/−] and Ahr [+/−] mice; these were miR-96 and miR-34C. [score:1]
Our data are not the first to report an increase in miR-135b. [score:1]
Cigarette smoke significantly increased miR-135b in the lungs of both Ahr [−/−] and Ahr [+/−] mice- consistent with the PCR array-but there was no significant difference in the level of miR-135b induction between Ahr [−/−] and Ahr [+/−] mice (Fig. 6D). [score:1]
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14
[+] score: 19
We found that the three ethanol-sensitive miRNAs with the highest average expression fold changes in the hippocampus, including the well-conserved miR-135a and miR-135b, were also significantly up-regulated in serum. [score:6]
Of the remaining validated ethanol-sensitive miRNAs, miR-135a and miR-135b are well-conserved and predicted to target Complexin 1 and Complexin 2 (TargetScan, Release 6.2), which are involved in modulating neurotransmitter release [40]. [score:5]
Four out of seven miRNAs, miR-135a, miR-135b, miR-467b-5p and miR-487b, were confirmed to be significantly up-regulated in ethanol-exposed mice (Fig.   4c). [score:4]
Three miRNAs, miR-135a, miR-135b and miR-467b-5p, were significantly up-regulated (≥twofold) in the ethanol-exposed group compared to controls (Fig.   5). [score:3]
Linear regression analysis showed significant linear relationships between the hippocampus and serum for miR-135a (R [2] = 0.84, P < 0.01), miR-135b (R [2] = 0.91, P < 0.001) and miR-467b-5p (R [2] = 0.60, P < 0.05) in ethanol-exposed mice only. [score:1]
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15
[+] score: 16
Furthermore, qPCR was performed again to validate the downregulated and upregulated expression of selected miRNAs that may be relevant to development and confirmed that miR-135, miR-302, miR-449a, miR-200b, miR-200c, miR-193b, miR-130, and miR-141 were downregulated, whereas miR-10a, miR-181, and miR-470 were upregulated by RA treatment (Fig 4C and 4D). [score:16]
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16
[+] score: 15
mmu-miR-142-3p mmu-miR-152 mmu-miR-135b mmu-miR-135a mmu-miR-34c mmu-miR-494 MicroCosm Bmal1 Bmal1, Rorβ - - Reverbα Bmal1, Rorβ TargetScan Bmal1 - - - - Bmal1, Clock MiRanda Bmal1 Bmal1, Rorα, Rorβ Rorα, Rorβ Rorα, Rorβ Per2 Bmal1, Per2, Rorβ Because recent findings indicate that despite their abundant expression in the cytoplasm, 18s and 28s rRNA are absent in RNA extracted from circulating exosomes [31], 18s rRNA levels were analyzed in serum and WBC fractions of blood samples collected from mice (n = 3–4) at ZT3 and ZT7 to confirm that the detected small RNAs reflect serum expression, rather than artifact associated with cellular lysis during sample preparation. [score:7]
mmu-miR-142-3p mmu-miR-152 mmu-miR-135b mmu-miR-135a mmu-miR-34c mmu-miR-494 MicroCosm Bmal1 Bmal1, Rorβ - - Reverbα Bmal1, Rorβ TargetScan Bmal1 - - - - Bmal1, Clock MiRanda Bmal1 Bmal1, Rorα, Rorβ Rorα, Rorβ Rorα, Rorβ Per2 Bmal1, Per2, Rorβ Because recent findings indicate that despite their abundant expression in the cytoplasm, 18s and 28s rRNA are absent in RNA extracted from circulating exosomes [31], 18s rRNA levels were analyzed in serum and WBC fractions of blood samples collected from mice (n = 3–4) at ZT3 and ZT7 to confirm that the detected small RNAs reflect serum expression, rather than artifact associated with cellular lysis during sample preparation. [score:7]
miR-142-3p, miR-152, miR-494, miR-135b, miR-135a and miR-34c were found in descending order of abundance in the serum (Fig. 1A). [score:1]
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[+] score: 13
Notably, miR-340 and miR-135b can also reduce Myc expression to the some extent (Figure 4N). [score:3]
In addition, miR-340 and miR-135 were also the potential miRNAs that can repress Myc expression. [score:3]
Subsequently, we constructed the miRNA expression vectors of those predicted miRNAs and named those as pCDH-mir34a, pCDH-mir34b, pCDH-mir34c, pCDH-mir340, and pCDH-mir135b. [score:3]
By combining our sequencing data with the predicted result, we selected miR-34a, miR-34b, miR-34c, miR-340, and miR-135b to conduct further research. [score:1]
In addition, Myc may also be the target of miR-340 and miR-135b, but this finding requires further investigation. [score:1]
48 h after transfection, miR-34a, miR-34b, and miR-34c showed approximately 50% reduction effect, whereas miR-340 and miR-135b showed approximately 20% reduction (Figure 4M). [score:1]
48 h after transfection, miR-34a, miR-34b, and miR-34c can reach a 30% to 40% reduction, and miR-340 and miR-135b also showed slight reduction on the luciferase activity of Myc reporter (Figure 4J). [score:1]
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18
[+] score: 12
Mature ID Fold Regulation miR-135b −2.6965 miR-363 −2.5995 miR-98 −2.543 miR-132 −2.355 miR-103 −2.1776 miR-99b −2.044 miR-135a −1.8734 let-7d −1.7861 miR-130a −1.6538 miR-152 −1.6246 miR-129-5p −1.6232 miR-298 −1.6169 miR-185 −1.6035 miR-214 −1.5746 miR-140 −1.5688 miR-134 −1.5667 miR-18b −1.5607 miR-194 −1.5509 let-7f −1.5107 miR-149 −1.51 A. Scatterplot showing relative expression of miRNAs by macroarray. [score:4]
We also note with interest that MCMV infection leads to the downregulation of certain miRNAs (miR-135b and miR-145 exhibit respectively 3.5-fold and 4.9-fold reduction), suggesting viral control of cellular miRNA production. [score:4]
Mature ID Fold Regulation miR-135b −2.6965 miR-363 −2.5995 miR-98 −2.543 miR-132 −2.355 miR-103 −2.1776 miR-99b −2.044 miR-135a −1.8734 let-7d −1.7861 miR-130a −1.6538 miR-152 −1.6246 miR-129-5p −1.6232 miR-298 −1.6169 miR-185 −1.6035 miR-214 −1.5746 miR-140 −1.5688 miR-134 −1.5667 miR-18b −1.5607 miR-194 −1.5509 let-7f −1.5107 miR-149 −1.51 Because miRNAs typically regulate translation in animal cells, we compared CXCL10 and STAT1 protein levels in both control and Dicer [d/d] animals and cells. [score:4]
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19
[+] score: 12
In fact, miR-125b, miR-126, miR-10b, miR-10a and miR-191 were underexpressed whereas miR-26b, miR-607 and miR-135b were overexpressed in cancer samples examined, in comparison with the gynecomastia samples. [score:5]
miR-125b, miR-126, miR-10b, miR-10a and miR-191 were underexpressed in cancer samples, whereas miR-26b, miR-607 and miR-135b were overexpressed. [score:5]
To confirm the results of microarray analysis, we performed quantitative real-time PCR analysis on a limited number of samples (19 cancer samples, five gynecomastia samples) using probes corresponding to miR-125b, miR-126, miR-10b, miR-10a, miR-191, miR-26b, miR-607 and miR-135b (Figure 2). [score:1]
analysisTo confirm the results of microarray analysis, we performed quantitative real-time PCR analysis on a limited number of samples (19 cancer samples, five gynecomastia samples) using probes corresponding to miR-125b, miR-126, miR-10b, miR-10a, miR-191, miR-26b, miR-607 and miR-135b (Figure 2). [score:1]
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20
[+] score: 11
Moreover, we previously analyzed the 3′-UTR of murine GATA-3, focusing on the target sequences of the miR-135 family, using TargetScan and found a binding site specific for miR-135a, a microRNA that appears to be downregulated during AR [11]. [score:8]
Notably, a previous computational investigation utilizing bioinformatics data indicated that simplex miRNA, including those in the miR-135 family, may have the ability to regulate the immune response by targeting GATA-3 and regulating the biased differentiation of T-helper 2 (Th2) cells observed during AR [10]. [score:3]
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21
[+] score: 10
Other miRNAs from this paper: hsa-mir-135b
Of note among the miRNAs that have recently been identified is the strong upregulation of miR-135b which has been found in invasive mammary BALB-neuT carcinomas; acting on its targets, midline 1 (MID1) and mitochondrial carrier homolog 2 (MTCH2), it regulates CSC stemness in vitro and cancer cell metastatization in vivo [49]. [score:7]
This newly unveiled role for miR-135b in mammary carcinogenesis, as observed in other tumors such as colon cancer [50], osteosarcoma [51], ependymoma [52], and hepatocellular carcinoma [53], can provide the basis for the exploration of miR-135b, MID1, and MTCH2's potential as new therapeutic targets in mammary carcinogenesis. [score:3]
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22
[+] score: 10
Similarly, in breast cancer cells, it has been shown that PTENP1 modulates the expression levels of HRASLS5 (HRAS-like suppressor family, member 5) mRNA through the binding of miR-135b, a microRNA that has not been yet reported as PTEN -targeting (13). [score:7]
Pseudogene Parental gene Other genes Shared microRNAs Context Reference Oncosuppressive pseudogenes PTENP1 PTEN miR-17, 19, 21, 26, and 214 families Prostate cancer(23) Melanoma(39) Endometrial cancer(44) ccRCC(15) Hepatocellular carcinoma(30) Gastric cancer(45)(40) PTENP1 HRASLS5 miR-135b Breast cancer(13) TUSC2P TUSC2 miR-17, 93, 299-3p, 520a, 608, and 661 Breast cancer(46) INTS6P1 INTS6 miR-17-5p Hepatocellular carcinoma(47) Oncogenic pseudogenes OCT4-pg4 OCT4 miR-145 Hepatocellular carcinoma(34) OCT4-pg5 OCT4 miR-145 Endometrial carcinoma(48) HMGA1P6 HMGA1 miR-15, 16, 214, and 761 Thyroid carcinoma(49) HMGA1P7 Pituitary tumors(50) CYP4Z2P CYP4Z1 miR-125a-3p, 197, 204, 211, and 1226 Breast cancer(51) BRAFP1 BRAF miR-30a, 182, 590, and 876 DLBCL(52) Braf-rs1 Braf miR-134, 543, and 653 Diffuse large B-cell lymphoma(52) Additionally, it has been shown that pseudogenes can act as ceRNAs not only for their parental genes but also for other genes (Figure 1K and Table 1). [score:3]
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23
[+] score: 9
In mouse ST2 MSCs, miR-125b inhibited osteoblast differentiation while miR-133 and miR-135 directly targeted Runx2 and Smad5 production, inhibiting the commitment of C2C12 MSCs into bone precursor cells [14], [15]. [score:8]
Although it has been reported that a number of miRNAs, miR-204/211 [13], miR-125b [14], miR-133 and miR-135 [15], miR-141 and miR-200a [16], and miR-29b [17], were involved in osteoblastic differentiation, a few papers have been reported with regard to the functions of miR-10a, miR-10b, miR-9-3p and miR-19b. [score:1]
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[+] score: 9
REST directly down-regulates a large number of genes at the transcriptional level, but also probably indirectly activates the expression of other genes at the post-transcriptional level via the repression of many noncoding targets (Conaco et al., 2006; Mortazavi et al., 2006; Wu and Xie, 2006; Visvanathan et al., 2007; Singh et al., 2008; Johnson et al., 2009), including several micro RNAs (miRNAs) considered to be brain-specific (such as miR9, miR124, miR132, miR135, miR139, and miR153; Figure 1). [score:9]
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[+] score: 9
However, at the late stage the target genes of miRNA mir-135b are changed to Ccdc88a, Cdh10, Cth, Pcdhb3, Rnf138, Trpc6, and Ttyh2. [score:3]
For example, at the early stage the target genes of miRNA mir-135b are Arhgef9, Car3, Ccdc88a, Cth, Dcx, Efnb3, Faah, Gabra4, Ints2, Mrps25, Ms4a6d, Myo18a, Pcdh18, Pus1, Sip1, Tnpo1, and Wdhd1. [score:3]
MiRNA overlap (Figure 5(c))We have found that there are five miRNAs participated in both the early and late stages: mmu-mir-200a, mmu-mir-200b, mmu-mir-135b, mmu-mir-494 and mmu-mir-503. [score:1]
The mir-135b, mir-503b and mir-94 are also found to have relationship with lung cancer [42- 44]. [score:1]
We have found that there are five miRNAs participated in both the early and late stages: mmu-mir-200a, mmu-mir-200b, mmu-mir-135b, mmu-mir-494 and mmu-mir-503. [score:1]
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[+] score: 8
Finally, the remaining 24 miRNA exhibited differential expression between tumor and parenchyma in both the absence and presence of cigarette smoke exposure, including 2 miRNA (mmu-miR-135b-5p, mmu-miR-1198-5p), whose expression levels increased in parenchyma but remained stable in tumor tissue following MS exposure, 5 miRNA (mmu-miR-21-5p, mmu-miR-31-5p, mmu-miR-146b-5p, mmu-miR-665-3p, mmu-miR-744-5p) that remained more highly expressed in tumors compared to parenchyma, and 17 miRNA with lower expression levels in tumors than in parenchyma, even upon cigarette smoke exposure (Figure 8). [score:8]
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[+] score: 7
Three miRNAs associated with human basal-type tumors (miR-135b, miR-505 and miR-155), and seven miRNAs associated with human luminal type tumors (let-7a, let-7f, miR-100, miR-130a, miR-152, miR-214 and miR-29b) are similarly expressed in mouse basal-like and luminal-type tumors, respectively. [score:3]
Comparison of expression levels between the data and the PCR results demonstrated a strong correlation between the two platforms for miR-107, -10b, -193, -200b, -494, -505, -7a, and let7f; a modest association for miR-30b, -412; and weak or no association with miR-135b, -155, and -301 (Additional file 4). [score:3]
miR-135b, miR-505 and miR-155 are expressed in both basal human and mouse mammary tumors and many basal -associated miRNAs have not been previously characterized. [score:1]
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[+] score: 7
The quantitative RT-PCR analysis confirmed that all four of the selected up-regulated hsa (Homo sapiens)-miRNAs (miR-205, miR-182, miR-135b, and miR-455-3p) were significantly up-regulated in NPC tissues (Fig. 1C). [score:7]
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[+] score: 6
Furthermore microRNA-135b (increased in obese males’ sperm) is a member of a family of microRNAs that target SIAH1, a protein essential to the first embryonic cell cleavage [57], and if its abundance is altered it has potential ramifications for the delayed cleavage observed for embryos fathered by males on the same HFD regimen [52– 54]. [score:3]
Furthermore microRNA-30a/microRNA-135b and microRNA-133b are also predicted to target DNMT3A and DNMT3B, respectively, for mRNA degradation. [score:3]
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[+] score: 6
In our in vivo study, the expression of miRNAs targeting Ras (let-7f, miR-135b, miR-143, miR-466h, miR-470, and miR-487b) was regulated in the lung of metformin -treated mice, along with another miRNA (miR-376c) playing an antioxidant role. [score:6]
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[+] score: 6
Linc-MD1 can sponge miR-133 and miR-135 away from their target mRNAs, thus upregulating MAML1 and MEF2C, respectively [58]. [score:6]
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32
[+] score: 6
Umezu et al. demonstrated that exosomes derived from multiple myeloma cells can transfer miR135b to endothelial cells to directly suppress factor-inhibiting hypoxia-inducible factor 1 (FIH-1), and activate HIF-1α via the HIF-FIH signaling pathway, leading to the overproduction of angiogenic cytokines such as VEGF, angiopoietin-1, and osteopontin, therefore resulted in endothelial cell migration, proliferation, and angiogenesis [50]. [score:6]
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33
[+] score: 6
The dysregulation of miRNAs in CRC has been reported using miRNA expression profiling studies with different miRNAs identified either as enhancers (miR-21, miR-31, miR-103, miR-107) or suppressors (miR-135, miR-145, miR-200c) in the initiation and evolution of tumor metastasis [8- 13]. [score:6]
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34
[+] score: 6
To identify the specific microRNA targeting GSK3 β, we used a neuronal cell line to test the regulatory effects of several potential candidates based on the 3′-untranslated region (3′-UTR) sequence of GSK3 β and previous studies, including microRNA-23b (miR-23b), microRNA-28a (miR-28a), microRNA-221 (miR-221), microRNA-135b (miR-135b), microRNA-101a (miR-101a), microRNA-26a (miR-26a) and microRNA-603 (miR-603). [score:6]
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35
[+] score: 5
Fan et al., showed that microRNA- 135b (“miR-135b”) expression similarly provokes AMPK signaling to inhibit Dex -induced oxidative damages in osteoblasts [9]. [score:5]
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36
[+] score: 5
Expression of miR-467a*, interestingly, was enriched only in the nucleus of LSK and promyelocytes, while expression of miR-135* and miR-142-3p did not appear to be nuclear-enriched in any myeloid population (Figure 5B). [score:5]
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37
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For instance, linc-MD1 is a muscle-specific intergenic lncRNA that acts as a sponge for miR-133 and miR-135, preventing their suppression of MAML1 and MEF2C and activating muscle-specific gene expression [6]. [score:5]
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The disruption of normal miRNA expression along the axis, such as that seen in some pathologies like miRNA-135b overexpression in colon cancer 55, may affect intestinal homeostasis and/or functions. [score:5]
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39
[+] score: 5
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-21, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-33a, hsa-mir-98, hsa-mir-29b-1, hsa-mir-29b-2, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-133a-1, mmu-mir-135a-1, mmu-mir-141, mmu-mir-194-1, mmu-mir-200b, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-203a, hsa-mir-211, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-200b, mmu-mir-300, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-141, hsa-mir-194-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, 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-21a, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-27a, mmu-mir-98, mmu-mir-326, rno-mir-326, rno-let-7d, rno-mir-343, rno-mir-135b, hsa-mir-200c, mmu-mir-200c, mmu-mir-218-1, mmu-mir-218-2, mmu-mir-33, mmu-mir-211, mmu-mir-29b-2, mmu-mir-135a-2, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-326, hsa-mir-135b, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, 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-21, rno-mir-26b, rno-mir-27b, rno-mir-27a, 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-33, rno-mir-98, rno-mir-126a, rno-mir-133a, rno-mir-135a, rno-mir-141, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-200b, rno-mir-203a, rno-mir-211, rno-mir-218a-2, rno-mir-218a-1, rno-mir-300, hsa-mir-429, mmu-mir-429, rno-mir-429, hsa-mir-485, hsa-mir-511, hsa-mir-532, mmu-mir-532, rno-mir-133b, mmu-mir-485, rno-mir-485, hsa-mir-33b, mmu-mir-702, mmu-mir-343, mmu-mir-466b-1, mmu-mir-466b-2, mmu-mir-466b-3, hsa-mir-300, mmu-mir-511, rno-mir-466b-1, rno-mir-466b-2, rno-mir-532, rno-mir-511, mmu-mir-466b-4, mmu-mir-466b-5, mmu-mir-466b-6, mmu-mir-466b-7, mmu-mir-466b-8, hsa-mir-3120, rno-mir-203b, rno-mir-3557, rno-mir-218b, rno-mir-3569, rno-mir-133c, rno-mir-702, rno-mir-3120, hsa-mir-203b, mmu-mir-344i, rno-mir-344i, rno-mir-6316, mmu-mir-133c, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-30f, mmu-let-7k, mmu-mir-3569, rno-let-7g, rno-mir-29c-2, rno-mir-29b-3, rno-mir-466b-3, rno-mir-466b-4, mmu-mir-203b
Cesana et al. showed that a long-intergenic ncRNA (lincRNA), linc-MD1, regulates muscle differentiation by interacting with two miRNAs, miR-135 and miR-133, which can bind to MAML1 and MEF2C to regulate their expression levels. [score:5]
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To explore whether other miRNAs and genes involved in germ cell development were altered in PGCs as consequence of VCZ exposure, we examined the expression of miR-21, miR-135*, miR-381 and miR-486 miRNAs. [score:4]
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Other miRNAs from this paper: mmu-mir-135a-1, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-135a-2
15, 46 Hence, miR-135 levels were upregulated after single and chronic FLX administrations, [47] suggesting that this microRNA may act as an endogenous homeostatic mechanism to maintain the physiological balance between SERT and 5-HT [1A]-autoreceptors. [score:4]
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[+] score: 4
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-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, mmu-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
The miRNA families that change expression in both mouse and human were: let-7, miR-7, miR-15, miR-101, miR-140, miR-152 (all validated by qPCR, P < 0.05), as well as miR-17, miR-34, miR-135, miR-144, miR-146, miR-301, miR-339, miR-368 (qPCR not performed). [score:3]
26E-0212mmu-miR-101b-3pmir-1010.297.791.72E-059.11E-0437mmu-miR-101a-3pmir-1010.2410.121.17E-031.92E-0250mmu-miR-107-3pmir-1030.228.773.24E-034.12E-0264mmu-miR-124-5pmir-1240.156.327.13E-037.09E-0233mmu-miR-301a-3pmir-1300.228.396.90E-041.29E-0259mmu-miR-130a-3pmir-1300.168.305.94E-036.44E-0252mmu-miR-135b-5pmir-1350.227.924.08E-034.99E-0274mmu-miR-136-5pmir-1360.229.061.09E-029. [score:1]
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Schaap-Oziemlak A. M. Raymakers R. A. Bergevoet S. M. Gilissen C. Jansen B. J. Adema G. J. Kogler G. le Sage C. Agami R. van der Reijden B. A. MicroRNA hsa-miR-135b regulates mineralization in osteogenic differentiation of human unrestricted somatic stem cells Stem. [score:2]
It was observed in other studies that miR-135b, -150, -370, -542-5p, -652, and -654 were highly expressed compared to osteoblasts [72, 73, 74]. [score:2]
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Other miRNAs from this paper: hsa-mir-135b
Previous data suggested that tumorigenesis of Tgfbr1/Pten 2c KO mice has evident papilloma stages, and high molecular expression of miR-135b regulates HIF-1α [32]. [score:4]
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miR-135b + + + +miR-135b expressed was increased in patients with post-surgery elevation of prostate-specific antigen (chemical relapse), as compared with patients with non-relapse disease [47]. [score:4]
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A muscle-specific lncRNA, linc-MD1, displays decoy activity for two specific miRNAs (miR-133 and miR-135) and regulates the expression of MAML1 and MEF2C in a molecular circuitry affecting the differentiation program [28]. [score:4]
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[+] score: 4
Similarly, miR-135b downregulated Ppm1e, the AMPK phosphatase [41– 43], to activate AMPK and protect cells from oxidative stress [25]. [score:4]
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More recently, Elkan-Miller et al. showed expression in the inner ear sensory epithelia and specifically in vestibular hair cells where it is regulated by miR-135b 8. One of the first in-depth proteomic analyses of mouse sensory cochlear epithelium by mass spectrometry confirmed the presence of PSIP1-P75 among cochlear proteins 26. [score:4]
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Neither the putative miR-135 binding sites in the second exon of linc-MD1, nor the described distal or proximal regulatory elements [9], identified by myogenin or myoD ChIP-seq approaches in C2C12 myocytes [8, 24], were affected by the targeting strategy. [score:4]
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Meanwhile miR-135b, miR-145b, miR-211, miR-3097, miR-3102 were significantly upregulated compared to that in wild type mouse lungs. [score:3]
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Expressions of miR-100 and miR-135b were also decreased in two of the four cell mo dels. [score:3]
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52
[+] score: 3
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-21, hsa-mir-22, hsa-mir-28, hsa-mir-29b-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-29b-1, mmu-mir-124-3, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-145a, mmu-mir-150, mmu-mir-10b, mmu-mir-195a, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-206, mmu-mir-143, hsa-mir-10a, hsa-mir-10b, hsa-mir-199a-2, hsa-mir-217, hsa-mir-218-1, hsa-mir-223, hsa-mir-200b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-150, hsa-mir-195, hsa-mir-206, mmu-mir-200a, 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-16-1, mmu-mir-16-2, mmu-mir-21a, mmu-mir-22, mmu-mir-29c, rno-let-7d, rno-mir-329, mmu-mir-329, rno-mir-331, mmu-mir-331, rno-mir-148b, mmu-mir-148b, rno-mir-135b, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-10a, mmu-mir-17, mmu-mir-28a, mmu-mir-200c, mmu-mir-218-1, mmu-mir-223, mmu-mir-199a-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7b, mmu-mir-217, hsa-mir-29c, hsa-mir-200a, hsa-mir-365a, mmu-mir-365-1, hsa-mir-365b, hsa-mir-135b, hsa-mir-148b, hsa-mir-331, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, 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-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-10a, rno-mir-10b, rno-mir-16, rno-mir-17-1, rno-mir-21, rno-mir-22, rno-mir-28, rno-mir-29b-1, rno-mir-29c-1, rno-mir-124-3, rno-mir-124-1, rno-mir-124-2, rno-mir-133a, rno-mir-143, rno-mir-145, rno-mir-150, rno-mir-195, rno-mir-199a, rno-mir-200c, rno-mir-200a, rno-mir-200b, rno-mir-206, rno-mir-217, rno-mir-223, dre-mir-7b, dre-mir-10a, dre-mir-10b-1, dre-mir-217, dre-mir-223, hsa-mir-429, mmu-mir-429, rno-mir-429, mmu-mir-365-2, rno-mir-365, dre-mir-429a, hsa-mir-329-1, hsa-mir-329-2, hsa-mir-451a, mmu-mir-451a, rno-mir-451, dre-mir-451, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-1-2, dre-mir-1-1, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-10b-2, dre-mir-16a, dre-mir-16b, dre-mir-16c, dre-mir-17a-1, dre-mir-17a-2, dre-mir-21-1, dre-mir-21-2, dre-mir-22a, dre-mir-22b, dre-mir-29b-1, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-133a-2, dre-mir-133a-1, dre-mir-133b, dre-mir-133c, dre-mir-143, dre-mir-145, dre-mir-150, dre-mir-200a, dre-mir-200b, dre-mir-200c, dre-mir-206-1, dre-mir-206-2, dre-mir-365-1, dre-mir-365-2, dre-mir-365-3, dre-let-7j, dre-mir-135b, rno-mir-1, rno-mir-133b, rno-mir-17-2, mmu-mir-1b, dre-mir-429b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-9b-2, rno-mir-133c, mmu-mir-28c, mmu-mir-28b, hsa-mir-451b, mmu-mir-195b, mmu-mir-133c, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-451b, mmu-let-7k, rno-let-7g, rno-mir-29c-2, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
Cortex let-7c-1, miR-10a, miR-21, miR-124a-1, miR-128a, miR-135b, miR-150, miR-199a, miR-217, miR-329, miR-451. [score:1]
Olfactory bulb let-7b, let-7c-1, let-7c-2, miR-10a, miR-16, miR-17, miR-21, miR-22, miR-28, miR-29c, miR-124a-1, miR-124a-3, miR-128a, miR-135b, miR-143, miR-148b, miR-150, miR-199a, miR-206, miR-217, miR-223, miR-29b-1, miR-329, miR-331, miR-429, miR-451. [score:1]
Brain stem let-7c-1, miR-17, miR-135b, miR-150, miR-199a, miR-218-1, miR-223, miR-329. [score:1]
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53
[+] score: 3
Such mechanism was shown for Th1-specific miR-135b 52 repressing Th2 -associated genes Stat6 and Gata3 mRNA translation to protein 53. [score:3]
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54
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The regulation of these miRNAs by REST was evaluated in embryonic striatal cell lines, and mir-29a, mir-124a, mir-132, and mir-135b were shown to be significantly upregulated upon loss of REST function and in the cortex of 12-week-old R6/2 mice. [score:3]
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55
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Therefore, the present study analyzed the 3′ UTR of mouse GATA-3 and miR-135 with TargetScan. [score:3]
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56
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The expression of 10 mature miRNAs (let7i, mir-21, mir-26a, mir-29a, mir-29b, mir-29c, mir-30d, mir-125b, mir-135b, mir-143) was analyzed by TaqMan qPCR from total RNA extracted from thyroids of 3-weeks Pax8-cDicer mutant mice and control mice (n = 2). [score:3]
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Other miRNAs from this paper: mmu-mir-132, mmu-mir-135a-1, mmu-mir-135a-2
The protein Gmps that was found deregulated in all analysis is shown with protein name, fold-changes, and protein variability using global proteomics approach (B); HT22 cells and hippocampus: n = 4 and cortex: n = 5. Figure S5, Visualisation of the fold changes of snoRNA135 and ΔCt values between miRNA-135 and snoRNA135 in control and irradiated cells and tissues. [score:2]
The columns represent the fold changes of snoRNA135 in miRNA normalisation (A, C, E) and ΔCt values of the differences between the Ct values of miRNA-135 and snoRNA135 (B, D, and F) with standard errors of the mean (SEM) in vitro (HT22 cells: n = 4 for 4 hours and 24 hours post-irradiation) and in vivo (hippocampus [H]: n = 3 for 24 hours post-irradiation; cortex [C]: n = 3 for 24 hours post-irradiation) experimental set-ups. [score:1]
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In cells with an activated MAPK/ERK pathway, the expression levels of let-7a, miR-10, miR-22, miR-26, miR-34, and miR-125a were lower, and those of miR-20, miR-25, and miR-135b, were higher (Supplementary Table 1). [score:3]
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Furthermore, miR-135 and miR-203 reduce tumor growth and metastasis of MD-MB-231 cells to the bones by targeting the runt-related transcription factor 2 (Runx2) [8]. [score:3]
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Other miRNAs from this paper: hsa-mir-135b
MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse mo del of head and neck squamous cell carcinoma. [score:2]
In previous studies, we proved that the angiogenesis in 2c KO mouse HNSCC is related to HIF-1α activation by miR-135b [19]. [score:1]
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STAT3 inhibited the activation of GATA3 and STAT6 through miR-135b in anaplastic large cell lymphoma [58]. [score:3]
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62
[+] score: 2
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-17, hsa-mir-21, hsa-mir-29a, hsa-mir-96, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-140, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-194-1, mmu-mir-200b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-181a-1, hsa-mir-200b, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-140, hsa-mir-194-1, 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-21a, mmu-mir-29a, mmu-mir-96, mmu-mir-34a, hsa-mir-200c, hsa-mir-181b-2, mmu-mir-17, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-376c, hsa-mir-376a-1, mmu-mir-376a, hsa-mir-135b, mmu-mir-181b-2, mmu-mir-376b, dre-mir-34a, dre-mir-181b-1, dre-mir-181b-2, dre-mir-182, dre-mir-183, dre-mir-181a-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-15a-1, dre-mir-15a-2, dre-mir-17a-1, dre-mir-17a-2, dre-mir-21-1, dre-mir-21-2, dre-mir-29a, dre-mir-96, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-140, dre-mir-181c, dre-mir-194a, dre-mir-194b, dre-mir-200b, dre-mir-200c, hsa-mir-376b, hsa-mir-181d, hsa-mir-507, dre-let-7j, dre-mir-135b, dre-mir-181a-2, hsa-mir-376a-2, mmu-mir-376c, dre-mir-34b, dre-mir-34c, mmu-mir-181d, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-let-7k, dre-mir-181a-4, dre-mir-181a-3, dre-mir-181a-5, dre-mir-181b-3, dre-mir-181d, mmu-mir-124b
Friedland et al. (2009) miR-135b PC4 and SFRS1 interacting protein 1 (Psip1-p75) Luciferase assay and qRT-PCR on Cal51, breast carcinoma, cells; inhibition of miR. [score:2]
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63
[+] score: 2
Click here for file Supplemental Figure S2: Validation of miR-135* and miR-199a-5a levels by qRT-PCR. [score:1]
Supplemental Figure S2: Validation of miR-135* and miR-199a-5a levels by qRT-PCR. [score:1]
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64
[+] score: 2
Linc-MD1 is required for appropriate muscle differentiation, at least in part because it regulates the levels of myocyte enhancer factor 2C (MEF2C) and mastermind-like protein 1 (MAML1) by sponging endogenous miR-133 and miR-135 in the cytoplasm of muscle cells [24]. [score:2]
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65
[+] score: 2
Other miRNAs from this paper: mmu-mir-17
This network shows that WAC is under regulatory control of NIR17, MIR135B, and MIR135A1. [score:2]
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66
[+] score: 2
Other miRNAs from this paper: hsa-mir-135b
Recently, it has been showed that multiple myeloma cells in chronic hypoxic bone marrow secrete more exosomes than the parental cells under normoxia; interestingly, exosomal miR-135b regulated the HIF-1 signaling in HUVECs by enhancing angiogenesis [37]. [score:2]
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67
[+] score: 2
Higher or lower levels of miR-135 can alter anxiety- and depression-like behaviors in mice via regulating activity of serotonergic (5HT) neurons, 5HT levels in blood and brain, and behavioral response to antidepressant treatment [45]. [score:2]
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68
[+] score: 2
Other miRNAs from this paper: hsa-mir-135b
Nezu Y, Hagiwara K, Yamamoto Y, Fujiwara T, Matsuo K et al (2016) miR-135b, a key regulator of malignancy, is linked to poor prognosis in human myxoid liposarcoma. [score:2]
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69
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A powerful way to determine miRNA function was provided by the mirBridge approach [31], which indicated that mmu-miR-135b and mmu-miR-146b regulate the transforming growth factor-beta (TGF beta) and the NFkB signaling pathways, respectively. [score:2]
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70
[+] score: 1
Other miRNAs from this paper: mmu-mir-146a, mmu-mir-21a, mmu-mir-21b, mmu-mir-21c
Examples of DE bins detecting regions around annotated miRNAs, found both in an intron (mir-135b, A) and an interegenic region (mir-146a, B). [score:1]
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71
[+] score: 1
Using the ViTa Database, the human homologs of miR-135b-5p, miR-147-3p, miR-31-5p, miR-379-5p, miR-7a-5p, as well as the miR-449 (-5p) and miR-34 (-5p) families, were predicted to bind to viral RNA segments of influenza A/Puerto Rico/8/34/Mount Sinai (H1N1). [score:1]
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72
[+] score: 1
The reaction mixtures were incubated at 16 °C for 30 min, 42 °C for 30 min, 85 °C for 5 min, and 4 °C for 30 s. The values were normalized for housekeeping miR135. [score:1]
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73
[+] score: 1
In colorectal cancer, high levels of miR-135b and low levels of miR-590-5p have been associated with clinical stage and survival 14, 19. [score:1]
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74
[+] score: 1
miR-191 and miR-135 are required for long-lasting spine remo delling associated with synaptic long-term depression. [score:1]
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75
[+] score: 1
As miR-135a and miR-135b only differs by one nucleotide in a non-seed region, miR-135a was selected for validation studies. [score:1]
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76
[+] score: 1
In NSCLC, only a few miRNAs were identified in metastasis, including miR-31 [21] and miR-135b [22]. [score:1]
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77
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These miRNAs include miR-135, miR-143/145, miR-189, and miR-204. [score:1]
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78
[+] score: 1
Such a scenario is supported by the fact that some non-coding RNAs have been shown to bind to miRNAs at functional level as demonstrated by an interaction of linc-MD1 with miR-133 and miR-135 [32]. [score:1]
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79
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These are mir-17, mir-22, mir-28, mir-32, mir-128b, mir-135b, mir-143, mir-151, mir-181b-2, mir-205, mir-213, mir-216 and mir-372. [score:1]
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