Wnt/β-catenin signaling induces the myomiRs miR-133b and miR-206 to suppress Pax7 and induce the myogenic differentiation program.

Autor: Cui S; Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.; Department of Physiology, Shandong University School of Medicine, Jinan, Shandong, China., Li L; Department of Biochemistry, Flinders University, College of Medicine and Public Health, Bedford Park, South Australia, Australia.; Department of Biochemistry, University of Adelaide, Adelaide, South Australia, Australia., Mubarokah SN; Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia., Meech R; Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2019 Aug; Vol. 120 (8), pp. 12740-12751. Date of Electronic Publication: 2019 Apr 04.
DOI: 10.1002/jcb.28542
Abstrakt: The downregulation of Pax7 expression is an essential requirement for adult muscle progenitor cell differentiation during muscle regeneration. We previously found that canonical Wnt signals drive myogenic differentiation by positively regulating the expression of myogenic target genes, and also by negatively regulating Pax7 expression. To better understand how Wnt signals repress Pax7 expression, we screened for Wnt-regulated microRNAs (miRNAs) that could target the Pax7 3'untranslated region (UTR). Using wild-type and β-catenin null primary mouse myoblasts, we identified several Wnt/β-catenin regulated miRNAs, the most abundant of which were miR-133b and miR-206. While miR-206 was previously identified as Pax7 regulator, miR-133b has never been shown to regulate the Pax7 transcript. We show here that miR-133b is a more potent inhibitor of Pax7 expression than miR-206, and that it acts via a site adjacent to the miR-206 binding site in the Pax7 3'UTR. The primary transcript encoding miR-133b/miR-206 is specifically induced by Wnt/β-catenin, while the miR-1/miR-133a transcript is not; moreover, Wnt signals increase the secretion of mature miR-133b/miR-206 into exosomes. Overall, we conclude that miR-133b and to a lesser degree miR-206, but not miR-1 or miR-133a, are key components of the canonical Wnt-mediated pathway that allows differentiation to proceed by relieving Pax7-mediated repression of the myogenic program. Secretion of these miRNAs into exosomes may allow them to directly control the differentiation of neighboring cells.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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