Abstract
SummaryThe proliferation, apoptosis, and differentiation of myoblasts are essential processes in skeletal muscle development. During this developmental process, microRNAs (miRNAs) play crucial roles. In our previous RNA-seq study (accession number GSE62971), we found that miR-16-5p was differentially expressed between fast and slow growth in chicken. In this study, we report that miR-16-5p could inhibit myoblast proliferation, promote myoblast apoptosis, and repress myoblast differentiation by directly binding to the 3′ UTR of SESN1, which is also differentially expressed. Overexpression of SESN1 significantly promoted the proliferation, inhibited apoptosis, and induced differentiation of myoblasts. Conversely, its loss of function hampered myoblast proliferation, facilitated myoblast apoptosis, and inhibited myoblast differentiation. Interestingly, we found SESN1 could regulate p53 by a feedback mechanism, thereby participating in the regulation of p53 signaling pathway, which suggests that this feedback is indispensable for myoblast proliferation and apoptosis. Altogether, these data demonstrated that miR-16-5p directly targets SESN1 to regulate the p53 signaling pathway, and therefore affecting myoblast proliferation and apoptosis. Additionally, SESN1 targets myogenic genes to control myoblast differentiation.
Highlights
Introduction Since the firstmicroRNA Lin-4 was discovered in nematode in 19931, and the function of miRNA let-7 was subsequently demonstrated[2], miRNAs began to attract the attention of researchers and subsequently they have become an intense and focused area of biological research
In our previous RNA-seq study, we found that both miR-16-5p16 and SENS117 were differentially expressed between White recessive rock (WRR) and XH chickens (Supplementary File 1)
In chicken primary myoblast (CPM), overexpression of miR-16-5p promoted p21 mRNA and protein expression, and significantly increased the number of cells that progressed to G0/G1 and reduced the number of S phase cells (Fig. 1c, e)
Summary
Introduction Since the firstmicroRNA (miRNA) Lin-4 was discovered in nematode in 19931, and the function of miRNA let-7 was subsequently demonstrated[2], miRNAs began to attract the attention of researchers and subsequently they have become an intense and focused area of biological research. The first evidence that miRNAs were involved in muscle development came from the accumulation of specific miRNAs in muscle cells[8]. Cai et al Cell Death and Disease (2018)9:367 new and 189 known miRNAs. Cai et al Cell Death and Disease (2018)9:367 new and 189 known miRNAs During this analysis, 17 differentially expressed miRNAs were found in broilers and laying hens that may be associated with muscle development. Through miRNA target prediction and network analysis, it was found that these miRNAs could affect muscle growth of broilers and layers by targeting Activin A Receptor Type 2B (ACVR2B)[9]. During the same developmental stage, miR-1623, miR-181b, let-7b, and miR-128 were differentially expressed in the skeletal muscle of dwarf and normal chickens[10]
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