MicroRNA-378a-5p inhibits the differentiation of cytotrophoblast into syncytiotrophoblast

MicroRNAs are expressed abundantly in the placenta throughout pregnancy. We have previously reported that miR-378a-5p promotes trophoblast cell proliferation and invasion. To further understand the role of miR-378a-5p during placental development, we determined if it may also regulate the differentiation of cytotrophoblast (CTB) into the syncytiotrophoblast (STB). Using BeWo cells, we found that miR-378a-5p was down-regulated during Forskolin-induced STB differentiation. Transfection of miR-378a-5p mimic into BeWo cells decreased the formation of multinucleated STB, mRNA levels of differentiation markers and E-cadherin levels. However, inhibition of endogenous miR-378a-5p by anti-miR-378a-5p increased cell fusion, induced STB marker gene expression and decreased E-cadherin levels. Luciferase reporter assay and real-time PCR analysis showed that CCNG2 is a target of miR-378a-5p. Taken together, these findings demonstrate that miR-378a-5p is a negative regulator of STB differentiation. This study also provides initial evidence that CCNG2 promotes trophoblast differentiation and may be involved in miR-378a-5p-regulated STB formation.