Inhibited Differentiation and Growth of Myocyte Associated With Sarcopenia: The Key Role of the lncRNA A430093F15Rik/microRNA-337-3p/Fam168a Pathway.

Abstract

Sarcopenia is a muscle disorder characterized by progressive loss of muscle mass, strength and function with ageing. Non-coding RNAs have been reported to be involved in the progression of sarcopenia. The current study aimed to investigate the pathogenesis of sarcopenia. Based on the bioinformatics analyses and RT-qPCR validation, the lncRNA A430093F15Rik was selected as the potential target involved in sarcopenia progression. Its expression level was up-regulated with ageing in mice but down-regulated with myogenesis in C2C12 cells. Modulating A430093F15Rik showed that the inhibition of the lncRNA contributed to the attenuation of sarcopenia such as increased cell viability and enhanced myogenesis, while the overexpression promoted disease progression. The downstream effector of A430093F15Rik, miR-337-3p, showed opposite function to the lncRNA, while Fam168a showed similar effects. Moreover, modulating both factors also confirmed their distinct roles during sarcopenia progression. The dual luciferase and RNA pulldown assays then verified the direct binding between A430093F15Rik and miR-337-3p, and miR-337-3p and Fam168a, representing a ceRNA regulatory mechanism between A430093F15Rik, miR-337-3p and Fam168a. The current study identified a novel lncRNA, A430093F15Rik, that is involved in the progression of sarcopenia by acting as a competitive endogenous RNA (ceRNA) to sponge miR-337-3p and regulate the expression of Fam168a.