Inhibition of the JNK/MAPK signaling pathway by myogenesis-associated miRNAs is required for skeletal muscle development.
Shu-Juan XieJun-Hao LiHua-Feng ChenYe-Ya TanShu-Rong LiuYin ZhangHui XuJian-Hua YangShun LiuLing-Ling ZhengMian-Bo HuangYan-Hua GuoQi ZhangHui ZhouLiang-Hu QuPublished in: Cell death and differentiation (2018)
Skeletal muscle differentiation is controlled by multiple cell signaling pathways, however, the JNK/MAPK signaling pathway dominating this process has not been fully elucidated. Here, we report that the JNK/MAPK pathway was significantly downregulated in the late stages of myogenesis, and in contrast to P38/MAPK pathway, it negatively regulated skeletal muscle differentiation. Based on the PAR-CLIP-seq analysis, we identified six elevated miRNAs (miR-1a-3p, miR-133a-3p, miR-133b-3p, miR-206-3p, miR-128-3p, miR-351-5p), namely myogenesis-associated miRNAs (mamiRs), negatively controlled the JNK/MAPK pathway by repressing multiple factors for the phosphorylation of the JNK/MAPK pathway, including MEKK1, MEKK2, MKK7, and c-Jun but not JNK protein itself, and as a result, expression of transcriptional factor MyoD and mamiRs were further promoted. Our study revealed a novel double-negative feedback regulatory pattern of cell-specific miRNAs by targeting phosphorylation kinase signaling cascade responsible for skeletal muscle development.
Keyphrases
- signaling pathway
- skeletal muscle
- pi k akt
- induced apoptosis
- single cell
- insulin resistance
- epithelial mesenchymal transition
- transcription factor
- cell therapy
- protein kinase
- poor prognosis
- rna seq
- magnetic resonance
- gene expression
- cell death
- binding protein
- genome wide
- adipose tissue
- mesenchymal stem cells
- small molecule
- endoplasmic reticulum stress