DNA methylation-mediated repression of miR-941 enhances Lysine (K)-specific demethylase 6B expression in hepatoma cells [Gene Regulation]

July 21st, 2014 by Zhang, P.-P., Wang, X.-l., Zhao, W., Qi, B., Yang, Q., Wan, H.-Y., Shuang, Z.-n., Liu, M., Li, X., Li, S., Tang, H.

MicroRNAs (miRNAs) have been shown to play important roles in carcinogenesis. However, their underlying mechanisms of action in hepatocellular carcinoma (HCC) are poorly understood. Recent evidence suggests that epigenetic silencing of miRNAs through tumor suppression by CpG island hypermethylation may be a common hallmark of human tumors. Here, we demonstrated that miR-941 was significantly downregulated in HCC tissues and cell lines and was generally hypermethylated in HCC. The overexpression of miR-941 suppressed in vitro cell proliferation, migration and invasion and inhibited the metastasis of HCC cells in vivo. Furthermore, the histone demethylase KDM6B (Lysine (K)-specific demethylase 6B) was identified as a direct target of miR-941 and was negatively regulated by miR-941. The ectopic expression of KDM6B abrogated the phenotypic changes induced by miR-941 in HCC cells. We demonstrated that miR-941 and KDM6B regulated the epithelial-mesenchymal transition (EMT) process and affected cell migratory/invasive properties.