| Autor: |
Lim S; Department of Health, Human Performance, and Recreation, Exercise Science Research Center, University of Arkansas, Fayetteville, Arkansas, United States., Lee DE; Department of Health, Human Performance, and Recreation, Exercise Science Research Center, University of Arkansas, Fayetteville, Arkansas, United States., Morena da Silva F; Department of Health, Human Performance, and Recreation, Exercise Science Research Center, University of Arkansas, Fayetteville, Arkansas, United States., Koopmans PJ; Department of Health, Human Performance, and Recreation, Exercise Science Research Center, University of Arkansas, Fayetteville, Arkansas, United States.; Cell and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, Arkansas, United States., Vechetti IJ Jr; Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States., von Walden F; Neuropediatrics, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden., Greene NP; Department of Health, Human Performance, and Recreation, Exercise Science Research Center, University of Arkansas, Fayetteville, Arkansas, United States.; Cell and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, Arkansas, United States., Murach KA; Department of Health, Human Performance, and Recreation, Exercise Science Research Center, University of Arkansas, Fayetteville, Arkansas, United States.; Cell and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, Arkansas, United States. |
| Abstrakt: |
MicroRNAs (miRs) control stem cell biology and fate. Ubiquitously expressed and conserved miR-16 was the first miR implicated in tumorigenesis. miR-16 is low in muscle during developmental hypertrophy and regeneration. It is enriched in proliferating myogenic progenitor cells but is repressed during differentiation. The induction of miR-16 blocks myoblast differentiation and myotube formation, whereas knockdown enhances these processes. Despite a central role for miR-16 in myogenic cell biology, how it mediates its potent effects is incompletely defined. In this investigation, global transcriptomic and proteomic analyses after miR-16 knockdown in proliferating C2C12 myoblasts revealed how miR-16 influences myogenic cell fate. Eighteen hours after miR-16 inhibition, ribosomal protein gene expression levels were higher relative to control myoblasts and p53 pathway-related gene abundance was lower. At the protein level at this same time point, miR-16 knockdown globally upregulated tricarboxylic acid (TCA) cycle proteins while downregulating RNA metabolism-related proteins. miR-16 inhibition induced specific proteins associated with myogenic differentiation such as ACTA2, EEF1A2, and OPA1. We extend prior work in hypertrophic muscle tissue and show that miR-16 is lower in mechanically overloaded muscle in vivo. Our data collectively point to how miR-16 is implicated in aspects of myogenic cell differentiation. A deeper understanding of the role of miR-16 in myogenic cells has consequences for muscle developmental growth, exercise-induced hypertrophy, and regenerative repair after injury, all of which involve myogenic progenitors. |
