MiR-320-3p Regulates the Proliferation and Differentiation of Myogenic Progenitor Cells by Modulating Actin Remodeling.

Wan Lee,Mai Thi Nguyen

doi:10.3390/ijms23020801

Abstract

Skeletal myogenesis is essential for the maintenance of muscle quality and quantity, and impaired myogenesis is intimately associated with muscle wasting diseases. Although microRNA (miRNA) plays a crucial role in myogenesis and relates to muscle wasting in obesity, the molecular targets and roles of miRNAs modulated by saturated fatty acids (SFA) are largely unknown. In the present study, we investigated the role of miR-320-3p on the differentiation of myogenic progenitor cells. Palmitic acid (PA), the most abundant dietary SFA, suppressed myogenic factors expression and impaired differentiation in C2C12 myoblasts, and these effects were accompanied by CFL2 downregulation and miR-320-3p upregulation. In particular, miR-320-3p appeared to target CFL2 mRNA directly and suppress the expression of CFL2, an essential factor for filamentous actin (F-actin) depolymerization. Transfection of myoblasts with miR-320-3p mimic increased F-actin formation and nuclear translocation of Yes-associated protein 1 (YAP1), a key component of mechanotransduction. Furthermore, miR-320-3p mimic increased myoblast proliferation and markedly impeded the expression of MyoD and MyoG, consequently inhibiting myoblast differentiation. In conclusion, our current study highlights the role of miR-320-3p on CFL2 expression, YAP1 activation, and myoblast differentiation and suggests that PA-inducible miR-320-3p is a significant mediator of muscle wasting in obesity.

Highlights

Skeletal myogenesis is a tightly regulated complex process required for maintaining muscle mass and integrity, which are essential for the appropriate physical and metabolic function of the body [1]
We confirmed the induction of miR-320-3p expression in the Palmitic acid (PA)-treated cells by Quantitative Real-Time PCR (qRT-PCR) (Figure 1E), and miR-320-3p was selected for further investigations in the regulation of cofilin 2 (CFL2) expression and myoblast differentiation
We investigated the role of miR-320-3p in myoblast proliferation and cell cycle progression

Summary

Introduction

Skeletal myogenesis is a tightly regulated complex process required for maintaining muscle mass and integrity, which are essential for the appropriate physical and metabolic function of the body [1]. Impairment of skeletal myogenesis provokes muscle wasting diseases that increase the risk of morbidity and mortality, especially in older people [2]. Muscle wasting is closely associated with various conditions that suppress myogenesis, including oxidative stress, apoptosis, and senescence [3]. Accumulating evidence suggests that microRNAs (miRNAs) modulated by SFA and obesity contribute to the pathogenesis of muscle wasting [6,7]. The molecular mechanism responsible for the regulation of myogenesis by SFA-induced miRNAs remains to be elucidated

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Discussion

Conclusion