Skeletal Muscle Myogenesis

Lnc-ORA[LncRNA]

miR-532-3p[miRNA]

IGF2BP2[mRNA]

skeletal muscle cells

Mus musculus (mouse)

J Biol Chem. 2021 Feb 3:100376. doi: 10.1016/j.jbc.2021.100376.

Lnc-ORA interacts with microRNA-532-3p and IGF2BP2 to inhibit skeletal muscle myogenesis.

qRT-PCR

Skeletal muscle is one of the most important organs of the animal body. Long noncoding RNAs (lncRNAs) play a crucial role in the regulation of skeletal muscle development via several mechanisms. We recently identified lnc-ORA in a search for lncRNAs that influence adipogenesis, finding it impacted adipocyte differentiation by regulating the PI3K/AKT/mTOR 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 (Dex)-induced muscle atrophy in vitro. Furthermore, adeno-associated virus 9 (AAV9)-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 homologue (PTEN) gene; the resultant changes in PTEN suppressed the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Additionally, lnc-ORA interacted with insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and reduced the stability of myogenesis genes such as myogenic differentiation 1 (MyoD) and myosin heavy chain (MyHC). Collectively, these findings indicate that lnc-ORA could be a novel underlying regulator of skeletal muscle development.