Expression of miR-381-3p is elevated in the retina of OIR mice, but the role in the retinal neovascularization is elusive，and its mechanism of action was investigated by vitreous injection of miR-381-3p antagomir
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PROVIDER: PRJNA964700 | ENA |
REPOSITORIES: ENA
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Project description:To investigate the mechanism of miR-381-3p in the OIR mice retinal tissues OIR mice.
2023-05-05 | GSE231376 | GEO
Project description:Multidrug resistance-associated protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is highly expressed in the kidney of mammals and responsible for renal elimination of various drugs. Adenosine deaminase acting on RNA 1 (ADAR1) has been reported to regulate gene expression through catalyzing adenosine-to-inosine (A-to-I) RNA editing. In this study, we found that the down-regulation of ADAR1 increased the expression of MRP4 in human renal cells at post-transcriptional level. The results of luciferase reporter assays and microarray analysis revealed that down-regulation of ADAR1 decreased the levels of miR-381-3p, which led to the up-regulation of MPR4 expression. Circular RNAs (circRNAs) are a kind of closed loop endogenous non-coding RNAs that play a critical role of gene expression by acting as miRNA sponges. ADAR1 repressed the biogenesis of circular RNA circHIPK3 by catalyzing A-to-I RNA editing, which changed the secondary structure of precursor of circHIPK3. In silico analysis suggested that circHIPK3 acted as a sponge of miR-381-3p. Indeed, overexpression of circHIPK3 up-regulated the expression of MRP4 through interfering with miR-381-3p. Our results provide the novel point of view for regulating mechanism of the expression of xenobiotic transporters through mediating the control of circRNA expression by RNA editing enzyme ADAR1.
2022-07-27 | GSE192692 | GEO
Project description:This is a prospective-retrospective study to determine if the expression of the miRNA’s miR-31-3p and miR-31-5p are prognostic of patient outcomes or predictive of the benefit from anti-EGFR therapy in stage III Colon Cancer. The present study will utilize FFPE tumor samples collected from patients enrolled in the PETACC-8 study conducted by the Fédération Francophone de Cancérologie Digestive (FFCD). This phase 3 clinical trial prospectively randomized fully resected stage III colon cancer patients to receive adjuvant treatment with either FOLFOX-4 plus cetuximab or FLOFOX-4 alone.
| 2260465 | ecrin-mdr-crc
Project description:Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks.
2017-03-29 | MSV000080762 | MassIVE
Project description:Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks. Experimental design for mass spectrometry SILAC experiments can be found at https://figshare.com/s/8e79f008e0e58ec6efc2 or https://doi.org/10.6084/m9.figshare.4888139
2016-08-12 | PXD002172 | Pride
Project description:Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ~1:200-500 and predisposes individuals to sudden death and heart failure. The mechanisms through which diverse HCM-causing mutations cause cardiac dysfunction remain mostly unknown and their identification may reveal new therapeutic avenues. MicroRNAs have emerged as critical regulators of gene expression and disease phenotype in various pathologies. We explored whether miRNAs could play a role in HCM pathogenesis and offer potential therapeutic targets. Methods and Results: Using high-throughput miRNA expression profiling and qPCR analysis in two distinct mouse models of HCM, we found that miR-199a-3p expression levels are upregulated in mutant mice compared to age- and treatment-matched wild-type mice. We also found that miR-199a-3p expression is enriched in cardiac non-myocytes compared to cardiomyocytes. When we expressed miR-199a-3p mimic in cultured primary cardiac non-myocytes and analyzed the conditioned media by proteomics, we found that several ECM proteins (e.g., TSP2, FBLN3, COL11A1, LYOX) were differentially expressed. We confirmed our proteomics findings by qPCR analysis of selected mRNAs and demonstrated that miR-199a-3p mimic expression in cardiac non-myocytes drives upregulation of ECM genes including Tsp2, Fbln3, Pcoc1, Col1a1 and Col3a1. To examine the role of miR-199a-3p in vivo, we inhibited its function using lock-nucleic acid (LNA)-based inhibitors (antimiR-199a-3p) in an HCM mouse model. Our results revealed that progression of cardiac fibrosis is attenuated when miR-199a-3p function is inhibited in mild-to-moderate HCM. Finally, guided by computational target prediction algorithms, we identified mRNAs Cd151 and Itga3 as direct targets of miR-199a-3p and have shown that miR-199a-3p mimic expression negatively regulates AKT activation in cardiac non-myocytes. Conclusions: Altogether, our results suggest that miR-199a-3p may contribute to cardiac fibrosis in HCM through its actions in cardiac non-myocytes. Thus, inhibition of miR-199a-3p in mild-to-moderate HCM may offer therapeutic benefit in combination with complementary approaches that target the primary defect in cardiac myocytes.
2024-01-26 | PXD042904 | Pride
Project description:Expression profiling of HEK293T cells transfected with miR-neg (negative control), miR-132 or miR-381 mimics and treated with forskolin for 0, 1 or 4hrs.
2011-07-01 | GSE24812 | GEO
Project description:Long non-coding RNAs (lncRNAs) play pivotal roles in diseases such as osteoarthritis (OA). However, knowledge of the biological roles of lncRNAs is limited in OA. We aimed to explore the biological function and molecular mechanism of HOTTIP in chondrogenesis and cartilage degradation. We used the human mesenchymal stem cell (MSC) model of chondrogenesis, in parallel with, tissue biopsies from normal and OA cartilage to detect HOTTIP, CCL3, and miR-455-3p expression in vitro. Biological interactions between HOTTIP and miR-455-3p were determined by RNA silencing and overexpression in vitro. We evaluated the effect of HOTTIP on chondrogenesis and degeneration, and its regulation of miR-455-3p via competing endogenous RNA (ceRNA). Our in vitro ceRNA findings were further confirmed within animal models in vivo. Mechanisms of ceRNAs were determined by bioinformatic analysis, a luciferase reporter system, RNA pull-down, and RNA immunoprecipitation (RIP) assays. We found reduced miR-455-3p expression and significantly upregulated lncRNA HOTTIP and CCL3 expression in OA cartilage tissues and chondrocytes. The expression of HOTTIP and CCL3 was increased in chondrocytes treated with interleukin-1β (IL-1β) in vitro. Knockdown of HOTTIP promoted cartilage-specific gene expression and suppressed CCL3. Conversely, HOTTIP overexpression reduced cartilage-specific genes and increased CCL3. Notably, HOTTIP negatively regulated miR-455-3p and increased CCL3 levels in human primary chondrocytes. Mechanistic investigations indicated that HOTTIP functioned as ceRNA for miR-455-3p enhanced CCL3 expression. Taken together, the ceRNA regulatory network of HOTTIP/miR-455-3p/CCL3 plays a critical role in OA pathogenesis and suggests HOTTIP is a potential target in OA therapy.
2019-08-12 | PXD014988 | Pride
Project description:Extracellular vesicles (EVs) play critical roles in regulating bone metastatic microenvironment through mediating intercellular communications. Here, we report a direct regulatory mode between tumor cells and osteoclasts in osteolytic metastasis of prostate cancer via vesicular miRNAs transfer. Combined analysis of miRNAs profiles both in tumor-derived small EVs (sEVs) and osteoclasts identified miR-152-3p as a potential osteolytic molecules. Further in vitro experiments showed that sEVs were enriched in miR-152-3p, which targets osteoclastogenic regulator MAFB. Blocking miR-152-3p in sEVs upregulated the expression of MAFB and impaired osteoclastogenesis in recipient osteoclasts. In vivo xenograft mouse model found that blocking of miR-152-3p in sEVs significantly rescued the loss of trabecular architecture, while systemic inhibition of miR-152-3p using antagomiR-152-3p reduced the osteolytic lesions of cortical bone while remaining the basic trabecular architecture. Together, our findings suggest that miR-152-3p carried by prostate cancer-derived sEVs deliver osteolytic signals from tumor cells to osteoclasts, facilitating osteolytic progression in bone metastasis.
2021-02-24 | GSE161419 | GEO
Project description:Expression profiling of HEK293T cells transfected with miR-neg (negative control), miR-132 or miR-381 mimics and treated with forskolin for 0, 1 or 4hrs. HEK293T cells were reverse transfected with the respective miRNA mimics. 72hrs post-transfection, cells were treated with forskolin for 0, 1 or 4hrs. Total RNA was then extracted. Expression profiling was carried out with Affymetrix arrays. Experiment was performed in duplicate. Total of 18 samples.
2011-07-01 | E-GEOD-24812 | biostudies-arrayexpress