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MiR-208b modulating skeletal muscle development and energy homoeostasis through targeting distinct targets.

ABSTRACT: Embryonic and neonatal skeletal muscles grow via the proliferation and fusion of myogenic cells, whereas adult skeletal muscle adapts largely by remodelling pre-existing myofibers and optimizing metabolic balance. It has been reported that miRNAs played key roles during skeletal muscle development through targeting different genes at post-transcriptional level. In this study, we show that a single miRNA (miR-208b) can modulate both the myogenesis and homoeostasis of skeletal muscle by distinct targets. As results, miR-208b accelerates the proliferation and inhibits the differentiation of myogenic cells by targeting the E-protein family member transcription factor 12 (TCF12). Also, miR-208b can stimulate fast-to-slow fibre conversion and oxidative metabolism programme through targeting folliculin interacting protein 1 (FNIP1) but not TCF12 gene. Further, miR-208b could active the AMPK/PGC-1a signalling and mitochondrial biogenesis through targeting FNIP1. Thus, miR-208b could mediate skeletal muscle development and homoeostasis through specifically targeting of TCF12 and FNIP1.

SUBMITTER: Fu L

PROVIDER: S-EPMC7237154 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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miR-208b modulating skeletal muscle development and energy homoeostasis through targeting distinct targets.

Fu Liangliang L Wang Heng H Liao Yinlong Y Zhou Peng P Xu Yueyuan Y Zhao Yunxia Y Xie Shengsong S Zhao Shuhong S Li Xinyun X

RNA biology 20200224 5

Embryonic and neonatal skeletal muscles grow via the proliferation and fusion of myogenic cells, whereas adult skeletal muscle adapts largely by remodelling pre-existing myofibers and optimizing metabolic balance. It has been reported that miRNAs played key roles during skeletal muscle development through targeting different genes at post-transcriptional level. In this study, we show that a single miRNA (miR-208b) can modulate both the myogenesis and homoeostasis of skeletal muscle by distinct t ...[more]

PMID: 32037961

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Project description:Skeletal muscle, the main source of animal meat products, contains muscle fiber as a key unit. It is well known that transformation takes place between different types of muscle fibers, however, the conversion mechanism is not clear. In a previous study, our lab has demonstrated that there is a decrease in type I muscle fibers and an increase in type IIB muscle fibers in skeletal muscle of myostatin gene-edited Meishan pigs. Very interestingly, we observed the down regulation of miR-208b expression and an increase in expression the predicted target gene Mettl8 (Methyltransferase like 8) in skeletal muscle of MSTN gene-edited Meishan pigs. These results reveal that there is a potential connection between the conversion of skeletal muscle fiber types and miR-208b and Mettl8 expression. In this study, we first explored the expression patterns of miR-208b and Mettl8 in skeletal muscle in Meishan pigs; and then C2C12 cells were used to simulate the development and maturation of muscle fibers. Our results indicated that Myh4 expression level decreased and Myh7 expression level increased following overexpression of miR-208b in C2C12 cells. We therefore speculate that miR-208b can promote the conversion of fast-twitch fibers to slow-twitch fibers. The targeting relationship between Mettl8 and miR-208b was confirmed by results obtained using dual luciferase assay, RT-qPCR, and WB analysis. Following the transfection of Mettl8 siRNA into C2C12 cells, we observed that Mettl8 expression decreased significantly while Myh7 expression increased and Myh4 expression decreased, indicating that Mettl8 promotes the conversion of slow muscle fibers to fast muscle fibers. Additionally, changes in skeletal muscle fiber types are observed in those mice where miR-208b and Mettl8 genes are knocked out. The miR-208b knockout inhibits the formation of slow muscle fibers, and the Mettl8 knockout inhibits the formation of fast muscle fibers. In conclusion, our research results show that miR-208b regulates the conversion of different muscle fiber types by inhibiting Mettl8 expression.

Project description:MicroRNAs serve an important role in the development of several diseases. Numerous genes regulate the skeletal muscle differentiation of C2C12 myoblasts. The role of miR‑760 in rheumatoid arthritis (RA) has not been reported, to the best of our knowledge. Therefore, the aim of the present study was to examine the role of miR‑760 in regulating skeletal muscle proliferation in RA. Potential genes functionally involved in the tarsal joint of a collagen‑induced RA model were identified using Gene Expression Omnibus. Reverse transcription‑quantitative PCR and western blot analyses were performed to determine the mRNA and protein expression levels. The proliferation, cell cycle progression and migration of C2C12 myoblasts were detected using Cell Counting Kit‑8, flow cytometry and wound‑healing assays, respectively. TargetScan was used to predict the potential target genes of miR‑760, and this was verified using a dual‑luciferase reporter assay. In the present study, myosin‑18b (Myo18b) expression was determined to be downregulated in the RA model. Silencing Myo18b decreased the proliferation, abrogated the cell cycle progression, and reduced the migration and differentiation of C2C12 myoblasts. Expression levels of cyclin‑dependent kinase 2, cyclin D1, matrix metalloproteinase (MMP)‑2, MMP‑9, myogenin and myosin heavy chain 6 were all decreased when Myo18b was silenced. Furthermore, overexpression of Myo18b induced opposing effects on C2C12 myoblasts. It was shown that Myo18b was a target gene of miRNA‑760. Overexpression of miR‑760 decreased proliferation, cell cycle progression, migration and differentiation in C2C12 myoblasts, and decreased the expression of Myo18b. The opposite results were observed when miR‑760 was downregulated. In conclusion, miR‑760 inhibited proliferation and differentiation by targeting Myo18b in C2C12 myoblasts. The results of the present study may contribute to understanding the mechanisms underlying RA skeletal muscle proliferation, and miR‑760/Myo18b may serve as potential targets for treating patients with RA.

Dataset Information

MiR-208b modulating skeletal muscle development and energy homoeostasis through targeting distinct targets.

Publications

miR-208b modulating skeletal muscle development and energy homoeostasis through targeting distinct targets.

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