E-MTAB-7079
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-7079 | ExpressionAtlas | 2019-01-16
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:RNA-seq analysis of MES-MM 98 and REN mesothelioma cell lines modulated for miR-24-3p expression
| PRJEB27991 | ENA
Project description:Micro (mi)RNAs not only play important roles in biological processes such as proliferation, metabolism, differentiation and apoptosis, but also in diseases such as cancers. We identified miRNAs with deregulated expression in Hodgkin lymphoma (HL) and investigated their role in the pathogenesis of HL. Small RNA sequencing revealed 84 significantly differentially expressed miRNAs in HL cell lines as compared to GC-B cells. Three upregulated miRNAs, miR-23a-3p, miR-24-3p and miR-27a-3p, were derived from one primary-miRNA transcript. Loss-of-function analysis for these miRNAs and their seed family members resulted in decreased growth upon miR-24-3p inhibition in three and of miR-27a/b-3p inhibition in one HL cell line. Apoptosis analysis indicated that the effect of miR-24-3p on cell growth is at least in part caused by an increase of apoptotic cells. Argonaute 2 (Ago2)-IP revealed 1,142 genes consistently targeted by miRNAs in at least three out of four HL cell lines. Furthermore, 52 out of the 1,142 genes were predicated targets of miR-24-3p. Functional annotation analysis revealed a function related to cell growth, cell death and/or apoptosis for 15 out of the 52 genes. Western blotting of the top-5 genes showed increased protein levels upon miR-24-3p inhibition for CDKN1B and MYC. In summary, we showed that miR-24-3p is upregulated in HL and its inhibition impaired cell growth possibly via targeting CDKN1B and MYC.
2017-02-26 | GSE92616 | GEO
Project description:Micro (mi)RNAs not only play important roles in biological processes such as proliferation, metabolism, differentiation and apoptosis, but also in diseases such as cancers. We identified miRNAs with deregulated expression in Hodgkin lymphoma (HL) and investigated their role in the pathogenesis of HL. Small RNA sequencing revealed 84 significantly differentially expressed miRNAs in HL cell lines as compared to GC-B cells. Three upregulated miRNAs, miR-23a-3p, miR-24-3p and miR-27a-3p, were derived from one primary-miRNA transcript. Loss-of-function analysis for these miRNAs and their seed family members resulted in decreased growth upon miR-24-3p inhibition in three and of miR-27a/b-3p inhibition in one HL cell line. Apoptosis analysis indicated that the effect of miR-24-3p on cell growth is at least in part caused by an increase of apoptotic cells. Argonaute 2 (Ago2)-IP revealed 1,142 genes consistently targeted by miRNAs in at least three out of four HL cell lines. Furthermore, 52 out of the 1,142 genes were predicated targets of miR-24-3p. Functional annotation analysis revealed a function related to cell growth, cell death and/or apoptosis for 15 out of the 52 genes. Western blotting of the top-5 genes showed increased protein levels upon miR-24-3p inhibition for CDKN1B and MYC. In summary, we showed that miR-24-3p is upregulated in HL and its inhibition impaired cell growth possibly via targeting CDKN1B and MYC.
2017-02-26 | GSE92615 | GEO
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: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: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:Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related death worldwide Unique mutational combinations can result in distinct changes to gene regulatory mechanisms leading to variability in the efficacy of available therapeutics. To work toward novel therapeutic strategies, it is important to understand the mechanisms by which unique combinations of mutations affect gene regulatory mechanisms. To that end, in this study, we generated RNA- and small RNA-seq data from Apc (A; n=3), Apc/Kras/p53 (AKP; n=1), B-catenin (B; n=5), B-catenin/Kras/p53 (BKP; n=1), Kras/Rspo3/p53 (KRP; n=2), Kras/Rspo3/p53/Smad4 (KRPS; n=4), Kras/Rspo3/Smad4 (KRS; n=3), Rspo3 (R; n=2) mutant mouse enteroids, and wild-type (WT; n=2) controls. From this analysis, we found that miR-24-3p is upregulated master miRNA regulator across mutational contexts. Functional studies identified miR-24-3p as a regulator of cell survival. Utilizing RNA- and leChRO-seq from HCT116 cells treated with a miR-24-3p inhibitor (n=3) or scramble control (n=3), we identified HMOX1 and PRSS8 as candidate miR-24-3p targets subject to post-transcriptional regulation by miR-24-3p.
2022-11-15 | GSE188212 | 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: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:Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin’s lymphoma (NHL). In cancers, tumour suppressive microRNAs may be silenced by DNA hypermethylation. By microRNA profiling, miR-155-3p was significantly upregulated upon demethylation treatment of MCL cell lines with 5-aza-2’-deoxycytidine (5-azadC). Methylation-specific PCR, verified by pyrosequencing, showed complete methylation of miR-155-3p in one MCL cell line (REC-1). 5-azadC treatment of REC-1 led to demethylation and re-expression of miR-155-3p. Over-expression of miR-155-3p led to increased sub-G1 apoptotic cells and reduced cellular viability, demonstrating its tumour suppressive properties. By luciferase assay, lymphotoxin-beta (LT-β) was validated as a miR-155-3p target. In 31 primary MCL, miR-155-3p was found hypermethylated in 6(19%) cases. To test if methylation of miR-155-3p was MCL-specific, miR-155-3p methylation was tested in an additional 191 B-cell, T-cell and NK-cell NHLs, yielding miR-155-3p methylation in 66(34.6%) including 36(27%) non-MCL B-cell, 24(53%) T-cell and 6(46%) of NK-cell lymphoma. Moreover, in 72 primary NHL samples with RNA, miR-155-3p methylation correlated with miR-155-3p downregulation (p=0.030), and LT-β upregulation (p=0.004). Collectively, miR-155-3p is tumour suppressive microRNA hypermethylated in MCL and other NHL subtypes. As miR-155-3p targets LT-β, which is an upstream activator of the non-canonical NF-kB signalling, miR-155-3p methylation is potentially important in lymphomagenesis
2014-08-31 | GSE57128 | GEO