miR-206 and -486 Induce Myoblast Differentiation by Downregulating Pax7

Abstract

The Pax7 transcription factor is required for muscle satellite cell biogenesis and specification of the myogenic precursor lineage. Pax7 is expressed in proliferating myoblasts but is rapidly downregulated during differentiation. Here we report that miR-206 and -486 are induced during myoblast differentiation and downregulate Pax7 by directly targeting its 3 untranslated region (UTR). Expression of either of these microRNAs in myoblasts accelerates differentiation, whereas inhibition of these microRNAs causes persistence of Pax7 protein and delays differentiation. A microRNA-resistant form of Pax7 is sufficient to inhibit differentiation. Since both these microRNAs are induced by MyoD and since Pax7 promotes the expression of Id2, an inhibitor of MyoD, our results revealed a bistable switch that exists either in a Pax7-driven myoblast state or a MyoD-driven myotube state.

MicroRNAs 206 and 21 Cooperate To Promote RAS–Extracellular Signal-Regulated Kinase Signaling by Suppressing the Translation of RASA1 and SPRED1

“…miR-206 has been well characterized in muscle cells, where it promotes skeletal muscle regeneration in response to injury (81)(82)(83). An in silico search for cancer-relevant influences of miR-206 identified regulation of MAPK signaling as a likely effector pathway with potential effects on RASA1 and SPRED1 (Tables 1 and 2).…”

MiR-206 Controls the Phenotypic Modulation of Pulmonary Arterial Smooth Muscle Cells Induced by Serum from Rats with Hepatopulmonary Syndrome by Regulating the Target Gene, Annexin A2

“…As one of the differentiation-related miRNAs, miR-206 has been demonstrated to play a crucial role in the process of cellular differentiation. Dey et al [25] showed that the differentiation and proliferation of myoblasts were modulated by miR-206 through its direct target, pax7. Inose et al [26] identified miR-206 as a key regulator of osteoblast differentiation, where it acts by inhibiting the expression of the connexin 43 gene.…”

Protein O-Fucosyltransferase 1 Expression Impacts Myogenic C2C12 Cell Commitment via the Notch Signaling Pathway

“…Consequently, the myogenic differentiation route is favored by the loss of Pax7 and by Myog induction. As Pax7 expression is negatively regulated by microRNAs (miRNAs) 1, 206, and 486, which are themselves controlled by MyoD expression in myoblast differentiation (58,59), a quantification of these miRNAs should be conducted in our cell lines.…”