Retinoid acid-induced microRNA-31-5p suppresses myogenic proliferation and differentiation by targeting CamkIIδ

Background: We previously reported that Wnt5a/CaMKII delta (calcium/calmodulin-dependent protein kinase II delta) pathway was involved in the embryonic tongue deformity induced by excess retinoic acid (RA). Our latest study found that the expression of miR-31-5p, which was predicted to target the 3'UTR of CamkII delta, was raised in the RA-treated embryonic tongue. Thus, we hypothesized that the excess RA regulated Wnt5a/CaMKII delta pathway through miR-31-5p in embryonic tongue. Methods: C2C12 myoblast line was employed as an in vitro model to examine the suppression of miR-31-5p on CamkII delta expression, through which RA impaired the myoblast proliferation and differentiation in embryonic tongue. Results: RA stimulated the expression of miR-31-5p in both embryonic tongue and C2C12 myoblasts. Luciferase reporter assay confirmed that the 3'UTR of CamkII delta was a target of miR-31-5p. MiR-31-5p mimics disrupted CamkII delta expression, C2C12 proliferation and differentiation as excess RA did, while miR-31-5p inhibitor partially rescued these defects in the presence of RA. Conclusions: Excess RA can stimulate miR-31-5p expression to suppress CamkII delta, which represses the proliferation and differentiation of tongue myoblasts.