Circular RNA circAtxn10 regulates skeletal muscle cell differentiation by targeting miR-143-3p and Chrna1 in C2C12 cells
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ABSTRACT:
PROVIDER: PRJNA1186060 | ENA |
REPOSITORIES: ENA
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Project description:Skeletal muscle differentiation is a complex process regulated by a network of genes and transcription factors. Recent studies have revealed the roles of circular RNAs (circRNAs) and microRNAs (miRNAs) in modulating gene expression during myogenesis. We investigated the interaction between circAtxn10, miR-143, and the nicotinic acetylcholine receptor subunit alpha 1 (Chrna1) in skeletal muscle differentiation using the C2C12 cell line. Our results demonstrate that circAtxn10 expression increases during myogenic differentiation and acts as a sponge for miR-143-3p through direct binding. We identified Chrna1 as a direct target of miR-143-3p through three binding sites in its 3'-UTR and showed that both miR-143-3p mimic and Chrna1 knockdown significantly impair myogenesis. Notably, Chrna1 overexpression dramatically enhanced myogenic marker expression and myotube formation. Our findings establish a regulatory axis involving circAtxn10, miR-143, and Chrna1 that plays a critical role in modulating skeletal muscle differentiation, providing new insights into the complex molecular mechanisms regulating myogenesis.
2025-09-03 | GSE281859 | GEO
Project description:To identify putative novel specific targets of miR-143-3p and miR-145-5p, we overexpressed these miRNAs in BRAFV600E mutant human M238P melanoma cells using synthetic mimics or a synthetic “negative” control mimic (miR-Neg). RNA samples were harvested 48 hours post-transfection and 2 independent experiments were carried out.
2021-12-29 | GSE171880 | GEO
Project description:Rationale: Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). microRNAs (miRNAs) show promise as disease markers due to their cell-type specific expression patterns and stability in peripheral blood. Objective: To identify circulating miRNAs associated with acute IS, determine their temporal course up to 90 days post-stroke, and explore their utility as an early diagnostic marker. Methods and Results: We used RNA sequencing to study expression changes of circulating miRNAs in a discovery sample of 20 IS patients and 20 matched healthy control subjects (HCs). We further applied qRT-PCR in independent samples for validation (40 IS patients and 40 matched controls), replication (200 IS patients, 100 HCs), and in 72 patients with transient ischemic attacks (TIA). Sampling of patient plasma was done immediately upon hospital arrival. We identified, validated, and replicated three differentially expressed miRNAs, which were upregulated in IS patients compared to both HCs (miR-125a-5p [1.8-fold; P=1.5x10-6], miR-125b-5p [2.5-fold; P=5.6x10-6], and miR-143-3p [4.8-fold; P=7.8x10-9]) and TIA patients (miR-125a-5p: P=0.003, miR-125b-5p: P=0.003, miR-143-3p: P=0.005). Longitudinal analysis of expression levels up to 90 days after stroke revealed a normalization to control levels for miR-125b-5p and miR-143-3p starting at day two, while miR-125a-5p remained elevated. Levels of all three miRNAs depended on platelet numbers in a platelet spike-in experiment, but were unaffected by chemical hypoxia in N2a cells and in experimental stroke models. In a random forest classification, miR-125a-5p, miR-125b-5p and miR-143-3p differentiated between HCs and IS patients with an area under the curve (AUC) of 0.90 (sensitivity: 85.6%; specificity: 76.3%), which was superior to multimodal cranial computed tomography obtained for routine diagnostics (sensitivity: 72.5%) and previously reported biomarkers of acute IS (neuron specific enolase: AUC=0.69, interleukin 6: AUC=0.82). Conclusions: A set of circulating miRNAs (miR-125a-5p, miR-125b-5p, miR-143-3p) associates with acute IS and might have clinical utility as an early diagnostic marker.
2018-02-22 | GSE110993 | GEO
Project description:We aimed to identify miRNAs and pathways specifically deregulated in adolescent and young adult (AYA) T-ALL patients. Small RNA-seq showed no major differences between AYA and pediatric T-ALL, but it revealed downregulation of miR-143-3p in T-ALL patients. Prediction algorithms identified several known and putative oncogenes targeted by this miRNA, including KRAS, FGF1, and FGF9. Pathway analysis indicated signaling pathways related to cell growth and proliferation, including FGFR signaling and PI3K-AKT signaling, with the majority of genes overrepresented in these pathways being predicted targets of hsa-miR-143-3p. By luciferase reporter assays, we validated direct interactions of this miRNA with KRAS, FGF1 and FGF9. In cell proliferation assays, we showed reduction of cell growth upon miR-143-3p overexpression in two T-ALL cell lines. Our study is the first description of the miRNA transcriptome in AYA T-ALL patients and the first report on tumor suppressor potential of miR-143-3p in T-ALL. Downregulation of this miRNA in T-ALL patients might contribute to enhanced growth and viability of leukemic cells. We also discuss the potential role of miR-143-3p in FGFR signaling. Although this requires more extensive validation, it might be an interesting direction, since FGFR inhibition proved promising in preclinical studies in various cancers.
2022-09-06 | E-MTAB-11987 | biostudies-arrayexpress
Project description:Skeletal muscle has a central role in whole body metabolism with myofibers that represent its functional units. These are differentiated cells with different contraction power and metabolic traits. Faster contracting myofibers preferentially use glucose as substrate for energy production, while slower use lipids. Myofibers can plastically change phenotypic traits in response to pathophysiological stimuli. Since post-transcriptional mechanisms should administer the changes of these post-mitotic cells, we demonstrated that miR-142-3p influences myofiber fuel availability and mitochondrial morphology. In vitro and in vivo experiments demonstrate that miR-142-3p regulates lipids utilization. We used microarrays to characterize the global changes in gene expression in C2C12 myoblasts due to over-expression of miR-142-3p.
2019-12-20 | GSE98327 | GEO
Project description:Skeletal muscle has a central role in whole body metabolism with myofibers that represent its functional units. These are differentiated cells with different contraction power and metabolic traits. Faster contracting myofibers preferentially use glucose as substrate for energy production, while slower use lipids. Myofibers can plastically change phenotypic traits in response to pathophysiological stimuli. Since post-transcriptional mechanisms should administer the changes of these post-mitotic cells, we demonstrated that miR-27a-3p influences myofiber fuel availability and mitochondrial morphology. In vitro and in vivo experiments demonstrate that miR-27a-3p regulates glycogen utilization. We used microarrays to characterize the global changes in gene expression in C2C12 myoblasts due to over-expression of miR-27a-3p.
2019-12-20 | GSE98326 | GEO
Project description:The aim of this study was to investigate the effect of hsa-miR-143-3p on global gene expression in T-cell acute lymphoblastic leukemia (T-ALL) and to unravel its direct target genes. For this purpose we selected Jurkat T-ALL cell line characterized by low expression of this miRNA. The cells were transduced either with pCDH-CMV-MCS-EF1_GFP_puro empty vector (System Biosciences) or pCDH-CMV-MCS-EF1_GFP pre-mir-143 vector, each variant in three biological replicates. Total RNA was isolated from each samples. Additionally, RISC complexes containing miRNAs bound to their target mRNAs were isolated by AGO2 immunoprecipitation and the obtained fraction of RISC-bound RNA was isolated from each sample. All 12 libraries (6 total RNA samples and 6 AGO2-RIP samples) were sequenced on Illumina NovaSeq6000 platform, in 2x150 mode, with a coverage of 60M paired reads/sample.
2024-08-31 | E-MTAB-13462 | biostudies-arrayexpress
Project description:Impact of miR-143-3p and miR-145-5p overexpression on human M238P melanoma cells
| PRJNA721324 | ENA
Project description:Osteoblasts are the only somatic cell type with bone-forming ability. While the cellular and molecular mechanisms underlying their differentiation and function have been identified, their dynamic control in vivo is unclear. By intravital multiphoton microscopy of live bone tissues of osteoblast fluorescent reporter mice, we visualized intact mature osteoblasts in vivo and found that they actively secrete and capture extracellular microvesicles. Microvesicles from mature osteoblasts contain the microRNA miR-143-3p, which inhibits osteoblast differentiation. Osteoblast-specific deletion of miR-143 increased bone formation and miR-143-deficient microvesicles induced recovery from bone defect. In sum, we report a novel mode of intercellular communication in vivo via microRNA-containing extracellular vesicles, which controls bone homeostasis.
2022-02-04 | GSE144512 | 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