miR-324-5p Inhibits C2C12 cell Differentiation and Promotes Intramuscular Lipid Deposition through lncDUM and PM20D1
| Autor: | Haigang Cao, Jie Wang, Xin'e Shi, Gongshe Yang, Yihao Liu, Xiaomin Zhou, Kuilong Huang, Xiaoyu Zhang, Xiao Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pm20d1 Cellular differentiation 03 medical and health sciences 0302 clinical medicine lipid Lipid droplet Drug Discovery Gene expression medicine Myocyte Gene knockdown Myogenesis Chemistry lcsh:RM1-950 Skeletal muscle differentiation musculoskeletal system Cell biology lcsh:Therapeutics. Pharmacology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis miR-324-5p Molecular Medicine Original Article C2C12 myoblast lncDum tissues C2C12 |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 22, Iss, Pp 722-732 (2020) |
| ISSN: | 2162-2531 |
| DOI: | 10.1016/j.omtn.2020.09.037 |
| Popis: | Skeletal muscle is an important metabolic organ of the body, and impaired skeletal muscle differentiation can result in a wide range of metabolic diseases. It has been shown that microRNAs (miRNAs) play an important role in skeletal muscle differentiation. The aim of this study was to investigate the role of mmu-miR-324-5p in the differentiation of C2C12 myoblasts and lipid droplet deposition in myotubes for future targeted therapies. We found that mmu-miR-324-5p was highly expressed in mouse skeletal muscle. Overexpression of miR-324-5p significantly inhibited C2C12 myoblast differentiation while promoting oleate-induced lipid accumulation and β-oxidation in C2C12 myoblasts. Conversely, inhibition of mmu-miR-324-5p promoted C2C12 myoblast differentiation and inhibited lipid deposition in myotubes. Mechanistically, mmu-miR-324-5p negatively regulated the expression of long non-coding Dum (lncDum) and peptidase M20 domain containing 1 (Pm20d1) in C2C12 myoblasts. Reduced lncDum expression was associated with a significant decrease in the expression of myogenesis-related genes. Knockdown of mmu-miR-324-5p increased the levels of lncDum and myogenesis-related gene expression. Following oleate-induced lipid deposition in C2C12 myoblasts, overexpression of mmu-miR-324-5p decreased the expression of Pm20d1 while increasing the expression of mitochondrial β-oxidation and long-chain fatty acid synthesis-related genes. In conclusion, we provide evidence that miR-324-5p inhibits C2C12 myoblast differentiation and promotes intramuscular lipid deposition by targeting lncDum and Pm20d1, respectively. Graphical Abstract This study identified miR-324-5p as a key factor that inhibits the differentiation of C2C12 myoblasts by targeting lncDum and promotes intramuscular lipid deposition in myotubes by inhibiting the expression of PM20D1, and it revealed a potential target for the future therapy of muscle-related diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|