Interleukin-6 modifies the expression profile of microRNA in rat primary skeletal muscle cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE126237 | GEO | 2019/11/22
REPOSITORIES: GEO
Similar Datasets
Project description:In the present study we examined the expression profile of microRNA in mouse 3T3-L1 adipocytes treated with IL-6, a known inflammatory cytokine and an adipo-myokine. The miRNA microarray analysis revealed increased expression of 9 miRNA species in adipocytes exposed to IL-6 (1 ng/ml) for 8 days of differentiation. In order to verify the microarray data, qRT-PCR analysis was performed to quantify miRNA expression and we confirmed the increased expression of miR-146b-3p (fold change =1.49±0.17). Using Target Scan database we found potential targets for these miRNAs with expression modified by IL-6 and focused our further interest on genes/proteins involved in cytoskeleton organization and vesicle transport regulation, that is: actin, dynein, myosin light chain kinase, Rab4a, and glucose transporter Glut4.
2022-02-28 | GSE168108 | GEO
Project description:In the present study we examined the expression profile of microRNA in rat primary skeletal muscle cells (RSkMC) treated with IL-8, a chemokine and an angiogenic factor, which is released in visceral adipose tissue, but also found in contracting skeletal muscles. The miRNA microarray analysis revealed increased expression of 5 miRNA species, which were not yet described in skeletal muscle, in RSkMC exposed to IL-8 (1 ng/ml) for 11 days of differentiation. In order to verify the microarray data, qRT-PCR analysis was performed to quantify miRNA expression. We confirmed the increased expression of miR-154-3p (fold change =1.91), miR-541-5p (fold change =1.36), miR-376c-3p (fold change =1.84), and miR-338-3p (fold change =1.6), whereas let-7a-1-3p did not show a significant change in expression, in comparison to control group. Using Target Scan database we found potential targets for all miRNAs with expression modified by IL-8 and focused our further interest on genes and pathways involved in skeletal muscle hypertrophy, that is: myocilin, PKB/Akt and FoxO3.
2019-04-25 | GSE117413 | GEO
Project description:iPSC-derived neurons were treated with mimics and inhibitors of the miRNAs miR-150-5p, hsa-mir-193a-3p and hsa-miR-19b-3p.
RNA-sequencing was then performed to examine the effects of miRNA up-regulation and inhibition.
| EGAD00001006844 | EGA
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: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:Plastin 3 (PLS3), encoded by PLS3, is a newly recognized regulator of bone metabolism and mutations in the encoding gene result in severe childhood-onset osteoporosis. Since an X chromosomal gene, PLS3 mutation-positive males are typically more severely affected while females portray normal to increased skeletal fragility. Despite the severe skeletal pathology, conventional metabolic bone markers tend to be normal and are thus insufficient in diagnosing or monitoring patients. Our study aimed to explore serum microRNA (miRNA) concentrations in subjects with defective PLS3 function to identify novel markers that could differentiate subjects according to mutation status and give insight into the molecular mechanisms by which PLS3 regulates skeletal health. We analyzed fasting serum samples for a custom-designed panel comprising 192 miRNAs in 15 mutation-positive (5 males, age range 8–76 years, median 41 years) and 14 mutation-negative (6 males, 8–69 years, 40 years) subjects from four Finnish families with different PLS3 mutations. We identified a unique miRNA expression profile in the mutation-positive subjects with seven significantly up- or downregulated miRNAs (miR-93-3p, miR-532-3p, miR-133a-3p, miR-301b-3p, miR-181c-5p, miR-203a-3p, miR-590-3p; p-values 0.004–0.044).
2020-06-22 | GSE142872 | GEO
Project description:Increasing evidence suggests that global downregulation of miRNA expression is a hallmark of human cancer, potentially due to defects in the miRNA processing machinery. In this study, we found that the protein expression of Argonaute 2 (AGO2), a key regulator of miRNA processing, was downregulated in colorectal cancer (CRC) tissues, which was also consistent with the findings of the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Furthermore, the correlation between the levels of AGO2 and epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) indicated that reduced levels of AGO2 promoted EMT in CRC. Low expression of AGO2 was an indicator of a poor prognosis among CRC patients. Knockdown of AGO2 in CRC cells promoted migration, invasion and metastasis formation in vitro and in vivo but had no influence on proliferation. To provide detailed insight into the regulatory roles of AGO2, we performed integrated transcriptomic, quantitative proteomic and microRNA sequencing (miRNA-seq) analyses of AGO2 knockdown cells and the corresponding wild-type cells and identified neuropilin 1 (NRP1) as a new substrate of AGO2 via miR-185-3p. Our data provided evidence that knockdown of AGO2 resulted in a reduction of miR-185-3p expression, leading to the upregulation of the expression of NRP1, which is a direct target of miR-185-3p, and elevated CRC cell metastatic capacity. Inhibition of NRP1 or treatment with a miR-185-3p mimic successfully rescued the phenotypes of impaired AGO2, which suggested that therapeutically targeting the AGO2/miR-185-3p/NRP1 axis may be a potential treatment approach for CRC.
2021-02-11 | PXD024171 | iProX
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:WNT signaling is fundamental to bone health and its aberrant activation leads to skeletal pathologies. A heterozygous missense mutation p.C218G in WNT1, a key WNT pathway ligand, leads to severe early-onset osteoporosis with multiple peripheral and spinal fractures. Despite the severe skeletal manifestations, conventional bone markers are normal in mutation-positive patients. The objective of this study was to find novel biomarkers that differentiate between WNT1 mutation-positive and -negative subjects. We evaluated serum levels of 192 miRNAs in 12 mutation-positive (median age 39 years, range 11-76 years) and 12 mutation-negative (35 years, range 9-59 years) subjects from two Finnish families. The results indicate significant differences in circulating miRNA profiles with 2 upregulated (miR-18a-3p, miR-223-3p) and 6 downregulated miRNAs (miR-22-3p, miR-31-5p, miR-34a-5p, miR-143-5p miR-423-5p, miR 423-3p) in the mutation-positive subjects. Three of these (miR-22-3p, miR-34a-5p, and miR-31-5p) are known inhibitors of WNT signaling: miR-22-3p and miR-34a-5p target WNT1 mRNA and miR-31-5p is predicted to bind to the WNT1 3’UTR. Our results suggest that the WNT1 mutation disrupts a feed-back regulation between these miRNAs and WNT1, providing new insights into the pathogenesis of WNT-related bone disorders. Future studies are warranted to explore the potential diagnostic and therapeutic applications of these findings in osteoporosis.
2018-03-29 | GSE103473 | 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. 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