MiR-27b Promotes Muscle Development by Inhibiting MDFI Expression

Abstract

Background/Aims: Skeletal muscle plays an essential role in the body movement. However, injuries to the skeletal muscle are common. Lifelong maintenance of skeletal muscle function largely depends on preserving the regenerative capacity of muscle. Muscle satellite cells proliferation, differentiation, and myoblast fusion play an important role in muscle regeneration after injury. Therefore, understanding of the mechanisms associated with muscle development during muscle regeneration is essential for devising the alternative treatments for muscle injury in the future. Methods: Edu staining, qRT-PCR and western blot were used to evaluate the miR-27b effects on pig muscle satellite cells (PSCs) proliferation and differentiation in vitro. Then, we used bioinformatics analysis and dual-luciferase reporter assay to predict and confirm the miR-27b target gene. Finally, we elucidate the target gene function on muscle development in vitro and in vivo through Edu staining, qRT-PCR, western blot, H&E staining and morphological observation. Result: miR-27b inhibits PSCs proliferation and promotes PSCs differentiation. And the miR-27b target gene, MDFI, promotes PSCs proliferation and inhibits PSCs differentiation in vitro. Furthermore, interfering MDFI expression promotes mice muscle regeneration after injury. Conclusion: our results conclude that miR-27b promotes PSCs myogenesis by targeting MDFI. These results expand our understanding of muscle development mechanism in which miRNAs and genes work collaboratively in regulating skeletal muscle development. Furthermore, this finding has implications for obtaining the alternative treatments for patients with the muscle injury.

Analysis of Transcriptome and miRNAome in the Muscle of Bamei Pigs at Different Developmental Stages

“…MDFI was enriched in "negative regulation of WNT signaling pathway". High expression of MDFI inhibits porcine muscle satellite cell proliferation and promotes their differentiation [39]. ASPN was enriched in "anatomic structure development".…”

Regulation of microRNAs in Satellite Cell Renewal, Muscle Function, Sarcopenia and the Role of Exercise

“…An additional regulatory feedback loop involving miRNAs in promoting satellite cells differentiation has been demonstrated to reduce MyoD family inhibitor (MDFI) expression. miR-27b has been shown to inhibit the proliferation of pig satellite cells and to promote their differentiation in vitro, through the suppression of MDFI [82]. MDFI hides the nuclear localization signal of MyoD family protein, leading to the accumulation of transcription factors in the cytoplasm.…”

miR-194-5p negatively regulates the proliferation and differentiation of rabbit skeletal muscle satellite cells

“…Zhang et al [13] found miR-143 promoted the differentiation of bovine SMSCs by targeting IGFBP5. miR-27b was identified as an activator of differentiation but an inhibitor of proliferation by targeting MDFI in porcine pig satellite cells [14]. Miao et al [15] proved that miR-194 functioned as a suppressor of the proliferation and migration of osteosarcoma cells.…”