The role of miR-199a-3p in epithelial to mesenchymal transition of keratinocytes
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ABSTRACT:
PROVIDER: PRJNA772117 | ENA |
REPOSITORIES: ENA
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Project description:We found that miR-199a-3p expression is decreased in cSCC biopsies and cell lines compared to normal skin biopsies or normal keratinocytes cell. To understand the role lost expression of miR-199a-3p might have in tumorigenesis of keratinocytes, we aimed to fine possible biochemical pathways and possible targets of miR-199a-3p in cSCC. In order do so, we overexpressed miR-199a-3p in cSCC and used microarrays to find global gene expression affected by miR-199a-3p.
2022-11-01 | GSE186031 | GEO
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:Whole transcriptome Identification of direct targets of miR-199a-5p and miR-424-3p using biotinylated pull-downs found that both miRNAs are likely to have a role in the cell cycle. HEK293T cells were transfected with biotinylated miRNAs (either miR-199a-5p or miR-424-3p). The miRNAs and target mRNA were pulled down with streptavidin and compared to the input control.
2013-12-02 | E-GEOD-40406 | biostudies-arrayexpress
Project description:To identify the relevant targets of the selected miRNAs, we assessed global transcriptome changes by deep-sequencing total neonatal mouse cardiomyocyte RNA after transfection with hsa-miR-590-3p or hsa-miR-199a-3p Four condition experiment; one replicate per condition; mouse neonatal cardiomyocytes transfected with cel-miR-67, hsa-miR-590-3p and hsa-miR-199a-3p; samples collected 72 hours after transfection
2012-10-13 | E-GEOD-41538 | biostudies-arrayexpress
Project description:To identify the genes targeted by miR-199a-3p in metastatic melanoma cells, we compared global gene expression in miR-199a-3p vs control miR transiently transfected cells by transcriptomic microarrays.
2019-06-10 | GSE123597 | GEO
Project description:To clarify the role of miR-199a-3p in HCC, we carried out a gene expression microarray analysis using HCC cell lines (HLE and HLF) transfected with a miR-199a-3p mimic or a negative control. We found that 819 genes were downregulated (>2-fold) by miR-199a-3p in both cell lines.
2018-09-23 | GSE110216 | GEO
Project description:Cutaneous squamous cell carcinoma (CSCC) is an epidermal skin cancer that evolves from normal epidermis along several pre-malignant stages. Previously we found specific miRNAs alterations in each step along these stages. miR-199a-3p expression decreases at the transition to later stages. A crucial step for epithelial carcinoma cells to acquire invasive capacity is the disruption of cell-cell contacts and the gain of mesenchymal motile phenotype, a process known as epithelial-to-mesenchymal transition (EMT). This study aims to study the role of decreased expression of miR-199a-3p in keratinocytes' EMT towards carcinogenesis. First, we measured miR-199a-3p in different stages of epidermal carcinogenesis. Then, we applied Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) assay to search for possible biochemical targets of miR-199a-3p and verified that Ras-associated protein B2 (RAP2B) is a bona-fide target of miR-199a-3p. Next, we analyzed RAP2B expression, in CSCC biopsies. Last, we evaluated possible mechanisms leading to decreased miR-199a-3p expression. miR-199a-3p induces a mesenchymal to epithelial transition (MET) in CSSC cells. Many of the under-expressed genes in CSCC overexpressing miR-199a-3p, are possible targets of miR-199a-3p and play roles in EMT. RAP2B is a biochemical target of miR-199a-3p. Overexpression of miR-199a-3p in CSCC results in decreased phosphorylated focal adhesion kinase (FAK). In addition, inhibiting FAK phosphorylation inhibits EMT marker genes' expression. In addition, we proved that DNA methylation is part of the mechanism by which miR-199a-3p expression is inhibited. However, it is not by the methylation of miR-199a putative promoter. These findings suggest that miR-199a-3p inhibits the EMT process by targeting RAP2B. Inhibitors of RAP2B or FAK may be effective therapeutic agents for CSCC.
| S-EPMC9741271 | biostudies-literature
Project description:To identify putative novel specific targets of miR-199-5p, miR-199a-3p and miR-214-3p, we overexpressed these miRNAs in human MRC5 pulmonary fibroblasts (CCL-171) using synthetic pre-miRNAs or a synthetic “negative” pre-miRNA control (miR-Neg). RNA samples were harvested 48 hours post-transfection and 3 independent experiments were carried out.
2019-04-11 | GSE97824 | GEO
Project description:Whole transcriptome Identification of direct targets of miR-199a-5p and miR-424-3p using biotinylated pull-downs found that both miRNAs are likely to have a role in the cell cycle.
2013-12-02 | GSE40406 | GEO
Project description:To identify the relevant targets of the selected miRNAs, we assessed global transcriptome changes by deep-sequencing total neonatal mouse cardiomyocyte RNA after transfection with hsa-miR-590-3p or hsa-miR-199a-3p
2012-10-13 | GSE41538 | GEO