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

Bo Liu, Chao Liu, Wei Cong, Nan Li, Nan Zhou, Yi Tang, Chao Wei, Han Bai, Ying Zhang, Jing Xiao

We previously reported that Wnt5a/CaMKIIδ (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 CamkIIδ, was raised in the RA-treated embryonic tongue. Thus, we hypothesized that the excess RA regulated Wnt5a/CaMKIIδ pathway through miR-31-5p in embryonic tongue. C2C12 myoblast line was employed as an in vitro model to examine the suppression of miR-31-5p on CamkIIδ expression, through which RA impaired the myoblast proliferation and differentiation in embryonic tongue. RA stimulated the expression of miR-31-5p in both embryonic tongue and C2C12 myoblasts. Luciferase reporter assay confirmed that the 3'UTR of CamkIIδ was a target of miR-31-5p. MiR-31-5p mimics disrupted CamkIIδ expression, C2C12 proliferation and differentiation as excess RA did, while miR-31-5p inhibitor partially rescued these defects in the presence of RA. Excess RA can stimulate miR-31-5p expression to suppress CamkIIδ, which represses the proliferation and differentiation of tongue myoblasts.