miR-124 targets GATA6 to suppress cholangiocarcinoma cell invasion and metastasis

Feng Tian, Jian Chen, Shuguo Zheng, Dajiang Li, Xin Zhao, Peng Jiang, Jianwei Li, Shuguang Wang

Our previous study showed that GATA6 plays important roles in cholangiocarcinoma (CCA) cell invasion and metastasis. However, the regulation mechanism of GATA6 in CCA is not clear. In this study, we studied the potential function of miR-124 in CCA and the mechanism of GATA6 regulation. The expression levels of miR-124 and GATA6 in cancerous tissues from 57 CCA patients was detected by RT-PCR and IHC. The impact of miR-124 on GATA6 expression in CCA cells was evaluated using cell transfection, xenotransplantation into nude mice and a luciferase reporter assay. miR-124 was decreased in 57 cancerous tissue samples compared with 38 matched paracancerous samples. The miR-124 level was inversely associated with lymph node involvement and distant metastasis. miR-124 significantly inhibited invasion and migration of CCA cells in vitro. Furthermore, miR-124 inhibited CCA cell metastasis in nude mice. miR-124 inhibited the luciferase activity of reporter genes containing the wild-type GATA6 3'-UTR, which was abrogated by mutation of the binding site. The protein levels of GATA6 were negatively regulated by miR-124. miR-124 expression was inversely associated with GATA6 in 57 cancerous samples. The miR-124-induced suppression of CCA invasion was abrogated by remedial expression of GATA6. GATA6 expression was decreased by miR-124 overexpression in liver masses from nude mice. Our data suggested that miR-124 decreases GATA6 expression by targeting its 3'-UTR, which in turn inhibits CCA invasion and metastasis.