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

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.

Palmitic Acid Inhibits Myogenic Activity and Expression of Myosin Heavy Chain MHC IIb in Muscle Cells through Phosphorylation-Dependent MyoD Inactivation

“…Several studies have examined the direct effects of PA on cultured myoblasts and myocytes. Similar to the findings of the present study, treatment of myoblasts with PA has been shown to inhibit myogenic cell differentiation and myotube maturation [ 21 , 22 , 39 , 40 ] and reduce type II myosin protein expression [ 41 ]. We further clarified the detailed mechanism by which PA treatment selectively inhibits the expression of specific MHC isoforms at a transcription level during myoblast differentiation.…”

“…Furthermore, PA has been shown to induce endoplasmic reticulum (ER) stress, which in turn triggers programmed cell death via apoptosis [ 19 , 20 ]. PA also regulates the expression of several microRNAs, thereby inhibiting myoblast differentiation and maturation into myofibers [ 21 , 22 ].…”

Clinical value of serum miR‐320‐3p expression in predicting the prognosis of sepsis‐induced acute kidney injury

“…As far as we know, this is the first study which investigates miR‐320‐3p expression in AKI. Previous research on miR‐320‐3p has focused on pulmonary hypertension, ischaemia/reperfusion injury and muscle wasting in obesity 10–12 . In this study, the death group showed greatly higher the levels of serum miR‐320‐3p, NGAL, KIM‐1 and the APACHE II mark than the survival group, suggesting that the levels of serum miR‐320‐3p, NGAL and KIM‐1 are related to the severity of sepsis complicated with AKI, and may take part in the appearance and growth of AKI.…”

“…Previous research on miR-320-3p has focused on pulmonary hypertension, ischaemia/reperfusion injury and muscle wasting in obesity. [10][11][12] In this study, the death group showed greatly higher the levels of serum miR-320-3p, NGAL, KIM-1 and the APACHE II mark than the survival group, suggesting that the levels of serum miR-320-3p, NGAL and KIM-1 are related to the severity of sepsis complicated with AKI, and may take part in the appearance and growth of AKI. Similarly, Hu X M et al displayed that serum NGAL and KIM-1 extents were significantly grown in the death group, and the combined detection of the two tests had good predictive value for neonatal renal injury with sepsis at 28d.…”

RNA-Seq Reveals miRNA and mRNA Co-regulate Muscle Differentiation in Fetal Leizhou Goats

“…More miRNAs have been implicated in muscle differentiation as research has progressed in recent years. MiR-320-3p was discovered to promote Factin accumulation by inhibiting CFL2, activating YAP1, and increasing myoblast proliferation, ultimately compromising myoblast differentiation (19). MiR-22-3p suppresses skeletal muscle cell proliferation while promoting cell differentiation in Hu sheep by targeting IGFBP3 (20).…”