Ectopic expression of microRNA-874 represses epithelial mesenchymal transition through the NF-κB pathway via CCNE1 in cholangiocarcinoma

Abstract

Cholangiocarcinoma (CC) is a devastating disease associated with poor survival rate. microRNAs (miRNAs) have recently been reported to assume a great role in CC development. This research aims to explore the functions of miR-874 in regulating epithelial mesenchymal transition (EMT) in CC. In obtained CC tissues and cells, miR-784 expression was assessed by RT-qPCR, and CCNE1 expression by RT-qPCR or immunohistochemistry. Dual-luciferase reporter assay was implemented for relationship between miR-784 and CCNE1. The roles of miR-784, CCNE1 and the NF-κB pathway in CC were investigated on human CC cell lines. CCNE1 was found to be highly expressed in CC while miR-874 expression was lowered in CC tissues and cells, thereby suggesting a negative regulatory effect of CCNE1. In QBC939 and RBE cells, overexpressing miR-874 or silencing CCNE1 led to augmented IκBα and E-cadherin expression, but diminished CCNE1, NF-κB, N-cadherin, and Vimentin expression. Moreover, overexpression of miR-874 or CCNE1 silencing led to reduced cell proliferation, invasion, and migration capabilities. In conclusion, we demonstrated that miR-874 negatively regulated CCNE1 to inhibit the NF-κB pathway, thus consequently suppressing EMT in CC. Therefore, the overexpression of miR-874 might bring favorable outcomes for the treatment of CC.