miR-145-3p Inhibits MuSCs Proliferation and Mitochondria Mass via Targeting MYBL1 in Jianzhou Big-Eared Goats

Muscle growth and injury-induced regeneration are controlled by skeletal muscle satellite cells (MuSCs) through myogenesis in postnatal animals. Meanwhile, myogenesis is accompanied by mitochondrial function and enzyme activity. Nevertheless, the underlying molecular mechanisms involving non-coding RNAs including circular RNAs (circRNAs) and microRNAs (miRNAs) remain largely unsolved. Here, we explored the myogenic roles of miR-145-3p and MYBL1 on muscle development and mitochondrial mass. We noticed that overexpression of miR-145-3p inhibited MuSCs proliferation and reduced the number of viable cells. Meanwhile, deficiency of miR-145-3p caused by LNAantimiR-145-3p or an inhibitor retarded the differentiation of MuSCs. miR-145-3p altered the mitochondrial mass in MuSCs. Moreover, miR-145-3p targeted and negatively regulated the expression of CDR1as and MYBL1. The knockdown of the MYBL1 using ASO-2'MOE modification simulated the inhibitory function of miR-145-3p on cell proliferation. Additionally, MYBL1 mediated the regulation of miR-145-3p on Vexin, VCPIP1, COX1, COX2, and Pax7. These imply that CDR1as/miR-145-3p/MYBL1/COX1, COX2, VCPIP1/Vexin expression at least partly results in a reduction in mitochondrial mass and MuSCs proliferation. These novel findings confirm the importance of mitochondrial mass during myogenesis and the boosting of muscle/meat development in mammals.

Automated summary

Muscle growth and injury-induced regeneration in postnatal animals are controlled by skeletal muscle satellite cells (MuSCs) through myogenesis. However, the molecular mechanisms involving non-coding RNAs, including circRNAs and miRNAs, are still unclear. In this study, the role of miR-145-3p and MYBL1 in muscle development and mitochondrial mass was investigated. The overexpression of miR-145-3p inhibited MuSCs proliferation, while its deficiency retarded MuSCs differentiation. miR-145-3p altered the mitochondrial mass in MuSCs and negatively regulated the expression of CDR1as and MYBL1. Knockdown of MYBL1 simulated the inhibitory function of miR-145-3p on cell proliferation. These findings confirm the importance of mitochondrial mass and the regulatory role of miR-145-3p and MYBL1 in muscle development.