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Published on: May 17, 2016
MiR-424-5p targets HSP90AA1 to facilitate proliferation and restrain differentiation in skeletal muscle development
Xi Chen1, Ying Zhu1,2, Chengchuang Song1
1School of Life Science, Institute of Cellular and Molecular Biology, Jiangsu Normal University, Xuzhou, China.
Abstract:
MiR-424-5p was found to be a potential regulator in the proliferation, migration, and invasion of various cancer cells. However, the effects and functional mechanism of miR-424-5p in the process of myogenesis are still unclear. Previously, using microRNA (miRNA) sequencing and expression analysis, we discovered that miR-424-5p was expressed differentially in the different skeletal muscle growth periods of Xuhuai goats. We hypothesized that miR-424-5p might play an important role in skeletal muscle myogenesis. Then, we found that the proliferation ability of the mouse myoblast cell (C2C12 myoblast cell line) was significantly augmented, whereas the C2C12 differentiation was repressed after increasing the expression of miR-424-5p. Mechanistically, HSP90AA1 presented a close interrelation with miR-424-5p, which was predicted as a target gene in the progression of skeletal muscle myogenesis, using transcriptome sequencing, dual luciferase reporter gene detection, and qRT-PCR. The silencing of HSP90AA1 obviously increased C2C12 proliferation and diminished differentiation, which is consistent with the ability of miR-424-5p in C2C12. Altogether, our findings indicated the role of miR-424-5p as a novel potential regulator via HSP90AA1 during muscle myogenesis progression.
Insights
MicroRNA-424-5p promotes skeletal muscle cell proliferation and inhibits differentiation by targeting HSP90AA1. This study reveals miR-424-5p
Area of Science:
- Molecular Biology
- Genetics
- Animal Science
Background:
- MicroRNA-424-5p (miR-424-5p) is implicated in cancer cell behavior.
- The role of miR-424-5p in skeletal muscle myogenesis remains largely unknown.
- Differential expression of miR-424-5p was observed during skeletal muscle growth in Xuhuai goats.
Purpose of the Study:
- To investigate the function and mechanism of miR-424-5p in skeletal muscle myogenesis.
- To explore the relationship between miR-424-5p and its potential target gene, HSP90AA1, in muscle development.
Main Methods:
- MicroRNA sequencing and expression analysis in goat skeletal muscle.
- Overexpression and knockdown experiments in mouse C2C12 myoblast cell line.
- Transcriptome sequencing, dual luciferase reporter gene assay, and qRT-PCR to validate gene targets.
Main Results:
- Increased miR-424-5p expression enhanced C2C12 myoblast proliferation and repressed differentiation.
- HSP90AA1 was identified as a direct target gene of miR-424-5p involved in myogenesis.
- Silencing HSP90AA1 mimicked the effects of miR-424-5p overexpression on C2C12 cells.
Conclusions:
- MiR-424-5p acts as a novel regulator in skeletal muscle myogenesis.
- The miR-424-5p/HSP90AA1 axis plays a significant role in controlling muscle cell proliferation and differentiation.
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