Lnc-ORA interacts with microRNA-532-3p and IGF2BP2 to inhibit skeletal muscle myogenesis
| Autor: | Que Zhang, Weijun Pang, Rui Cai, Wenlong Yong, Yingqian Wang, Rui Zhao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
IGF2BP2 insulin-like growth factor 2 mRNA-binding protein 2 0301 basic medicine Myoblast proliferation Muscle Fibers Skeletal lnc-ORA obesity-related lncRNA lncRNAs long noncoding RNAs Muscle Development MyoD Biochemistry Myoblasts MAFbx muscle atrophy F-box Mice AAV adeno-associated virus Myosin Myocyte MyoG myogenin Adipogenesis Myogenesis MyoD myogenic differentiation 1 RNA-Binding Proteins Cell Differentiation RIP RNA immunoprecipitation insulin-like growth factor 2 mRNA-binding protein 2 Muscle atrophy Cell biology Muscular Atrophy medicine.anatomical_structure miR-532-3p RNA Long Noncoding myogenesis medicine.symptom Signal Transduction Research Article MyHC myosin heavy chain Biology KEGG Kyoto Encyclopedia of Genes and Genomes Dex dexamethasone 03 medical and health sciences GO Gene Ontology medicine Animals lnc-ORA skeletal muscle Muscle Skeletal silnc-ORA siRNA-lnc-ORA Molecular Biology Myogenin Cell Proliferation MuRF1 muscle RING finger 1 030102 biochemistry & molecular biology Skeletal muscle Cell Biology GAS gastrocnemius PTEN phosphatase and tensin homolog Mice Inbred C57BL MicroRNAs PTEN/PI3K/AKT signaling pathway 030104 developmental biology EdU 5-ethynyl-20-deoxyuridine MRFs myogenic regulatory factors Proto-Oncogene Proteins c-akt |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.100376 |
| Popis: | Skeletal muscle is one of the most important organs of the animal body. Long noncoding RNAs play a crucial role in the regulation of skeletal muscle development via several mechanisms. We recently identified obesity-related lncRNA (lnc-ORA) in a search for long noncoding RNAs that influence adipogenesis, finding it impacted adipocyte differentiation by regulating the PI3K/protein kinase B/mammalian target of rapamycin pathway. However, whether lnc-ORA has additional roles, specifically in skeletal muscle myogenesis, is not known. Here, we found that lnc-ORA was significantly differentially expressed with age in mouse skeletal muscle tissue and predominantly located in the cytoplasm. Overexpression of lnc-ORA promoted C2C12 myoblast proliferation and inhibited myoblast differentiation. In contrast, lnc-ORA knockdown repressed myoblast proliferation and facilitated myoblast differentiation. Interestingly, silencing of lnc-ORA rescued dexamethasone-induced muscle atrophy in vitro. Furthermore, adeno-associated virus 9–mediated overexpression of lnc-ORA decreased muscle mass and the cross-sectional area of muscle fiber by upregulating the levels of muscle atrophy–related genes and downregulating the levels of myogenic differentiation–related genes in vivo. Mechanistically, lnc-ORA inhibited skeletal muscle myogenesis by acting as a sponge of miR-532-3p, which targets the phosphatase and tensin homolog gene; the resultant changes in phosphatase and tensin homolog suppressed the PI3K/protein kinase B signaling pathway. In addition, lnc-ORA interacted with insulin-like growth factor 2 mRNA-binding protein 2 and reduced the stability of myogenesis genes, such as myogenic differentiation 1 and myosin heavy chain. Collectively, these findings indicate that lnc-ORA could be a novel underlying regulator of skeletal muscle development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|