miR-377 Inhibits Proliferation and Differentiation of Bovine Skeletal Muscle Satellite Cells by Targeting FHL2

Abstract

Non-coding RNAs, especially microRNAs (miRNAs), play an important role in skeletal muscle growth and development. miR-377 regulates many basic biological processes and plays a key role in tumor cell proliferation, migration and apoptosis. Nevertheless, the function of miR-377 during skeletal muscle development and how it regulates skeletal muscle satellite cells (SMSCs) remains unclear. In the present study, we proposed to elucidate the regulatory mechanism of miR-377 in the proliferation and differentiation of bovine primary SMSCs. Our results showed that miR-377 can significantly inhibit the proliferation of SMSCs. In addition, we found that miR-377 can reduce myotube formation and restrain skeletal myogenic differentiation. Moreover, the results obtained from the biosynthesis and dual luciferase experiments showed that FHL2 was the target gene of miR-377. We further probed the function of FHL2 in muscle development and found that FHL2 silencing significantly suppressed the proliferation and differentiation of SMSCS, which is contrary to the role of miR-377. Furthermore, FHL2 interacts with Dishevelled-2 (Dvl2) to enable Wnt/β-catenin signaling pathway, consequently regulating skeletal muscle development. miR-377 negatively regulates the Wnt/β-catenin signaling pathway by targeting FHL2-mediated Dvl2. Overall, these findings demonstrated that miR-377 regulates the bovine SMSCs proliferation and differentiation by targeting FHL2 and attenuating the Wnt/β-catenin signaling pathway.

The Role of MicroRNA in the Pathogenesis of Duchenne Muscular Dystrophy

“…Intriguingly, the differentiation, proliferation, and viability of muscle satellite cells are also regulated by miRNAs. For example, the activity of these cells is mediated by miR-381 [ 70 ], miR-378 [ 71 ], and miR-377 [ 72 ], among many miRNAs. Perhaps manipulation of miRNAs that regulate the viability and functionality of satellite cells could enhance dystrophic muscle regeneration.…”

Tissue engineering approaches for dental pulp regeneration: The development of novel bioactive materials using pharmacological epigenetic inhibitors

“…Consequently, β-catenin is stabilised and can translocate into the nucleus, which associates with TFs to upregulate target gene expression [ 381 ]. Furthermore, luciferase assays reveal that FHL2 is a target of miR-377, which attenuates Wnt/β-catenin signalling [ 382 ]. Investigating whether the adverse effects associated with SAHA treatment can be directly attributed to the upregulation of miR-377 isoforms via knockdown experiments would be valuable for understanding the underlying mechanisms.…”

The Function and Regulation Mechanism of Non-Coding RNAs in Muscle Development

“…miR-148a-3p down-regulates mesenchymal homology box 2 (Meox2), activates the PI3K/AKT signaling pathway, promotes SMSC differentiation, and inhibits apoptosis [60]. In calves this includes miR-377, miR-23a, and miR-2425-5p, and the mechanism of action is as follows: miR-377 targets FHL2 and attenuates the Wnt/β-catenin signaling pathway to inhibit the proliferation and differentiation of SMSCs [65]. miR-23a promotes myogenic differentiation of fetal bovine skeletal muscle-derived progenitor cells by targeting the MyoD family inhibitor structural domain-containing (MDFIC) genes [66].…”