miR-378a-3p responds to physical activity by modulating insulin-mediated glucose uptake and tricarboxylic acid cycle in skeletal muscle

Aerobic exercise training alters gene expression in skeletal muscle,and miRNAs significantly contribute to motion response.However,the molecular mechanisms by which miRNAs regulate the response to exercise training are not well understood.Here,we found that the abundance of miR-378a-3p in skeletal muscle significantly decreased after exercise training.miR-378a-3p knockout mice showed increased insulin sensitivity,insulin-mediated glucose uptake.

MiR-743a-5p regulates differentiation of myoblast by targeting Mob1b in skeletal muscle development and regeneration

The microRNAs (miRNAs) play an important role in regulating myogenesis by targeting mRNA. However, the understanding of miRNAs in skeletal muscle development and diseases is unclear. In this study, we firstly performed the transcriptome profiling in differentiating C2C12 myoblast cells. Totally, we identified 187 miRNAs and 4260 mRNAs significantly differentially expressed that were involved in myoblast differentiation. We carried out validation of microarray data based on 5 mRNAs and 5 miRNAs differentially expressed and got a consistent result. Then we constructed and validated the significantly up- and down-regulated mRNA-miRNA interaction networks. Four interaction pairs (miR-145a-5p-Fscn1, miR-200c-5p-Tmigd1, miR-27a-5p-Sln and miR-743a-5p-Mob1b) with targeted relationships in differentiated myoblast cells were demonstrated. They are all closely related to myoblast development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated cell cycle signals important for exploring skeletal muscle development and disease. Functionally, we discovered that miR-743a targeting gene Mps One Binder Kinase Activator-Like 1B (Mob1b) gene in differentiated C2C12. The up-regulated miR-743a can promote the differentiation of C2C12 myoblast. While the down-regulated Mob1b plays a negative role in differentiation. In addition, the expression profile of miR-743a and Mob1b are consistent with skeletal muscle recovery after Cardiotoxin (CTX) injury. Our study revealed that miR-743a-5p regulates myoblast differentiation by targeting Mob1b involved in skeletal muscle development and regeneration. Our findings made a further exploration for mechanisms in myogenesis and might provide potential possible miRNA-based target therapies for skeletal muscle regeneration and disease in the near future.

Single-cell analysis reveals the lncRNA-MEG3/miRNA-133a-3p/PRRT2 axis regulates skeletal muscle regeneration and myogenesis

Skeletal muscle is the largest motor and metabolic organ of the body, which has a robust capacity for regeneration following injury or disease. Delayed regeneration after skeletal muscle injury reduces muscle contractility and leads to dysfunction of innervation. Therefore, identifying the regulation components in skeletal muscle regeneration and determining their molecular mechanisms are important to discover novel therapeutic markers for muscular diseases. Long non-coding RNA (LncRNA) has been implicated in skeletal muscle regeneration. Recent developed single-cell RNA sequencing (scRNA-seq) provides a higher resolution of cellular differences than bulk RNA-seq. Here, we re-analyzed single-cell transcriptomes data of skeletal muscle regeneration and identified lncRNA maternally expressed gene 3 (lncRNA-MEG3) was highly expressed in muscle satellite cells (MuSCs). Further study showed that lncRNA-MEG3 regulates skeletal muscle regeneration via sponging miR-133a-3p to regulate proline-rich transmembrane protein 2 (PRRT2) expression level. These results suggested that lncRNA-MEG3 might be a potential target for skeletal muscle diseases.