Journal
CELL DEATH AND DIFFERENTIATION
Volume 25, Issue 9, Pages 1581-1597Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41418-018-0063-1
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Funding
- National Natural Science Foundation of China [31230042, 31471223, 81070589, 31701116]
- project of Science and Technology of Guangzhou [201504010022]
- National Key R&D Program of China from the Ministry of Science and Technology of China [2017YFA0504400]
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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.
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