%0 Journal Article
%1 xie2018let7c
%A Xie, Y
%A Zhang, H
%A Guo, X J
%A Feng, Y C
%A He, R Z
%A Li, X
%A Yu, S
%A Zhao, Y
%A Shen, M
%A Zhu, F
%A Wang, X
%A Wang, M
%A Balakrishnan, A
%A Ott, M
%A Peng, F
%A Qin, R Y
%D 2018
%E Dis, Cell Death
%J Cell Death & Disease
%K Ott
%N 2
%P 249
%T Let-7c inhibits cholangiocarcinoma growth but promotes tumor cell invasion and growth at extrahepatic sites
%V 9
%X Cholangiocarcinoma (CCA) is a cancer type with high postoperative relapse rates and poor long-term survival largely due to tumor invasion, distant metastasis, and multidrug resistance. Deregulated microRNAs (miRNAs) are implicated in several cancer types including CCA. The specific roles of the miRNA let-7c in cholangiocarcinoma are not known and need to be further elucidated. In our translational study we show that microRNA let-7c expression was significantly downregulated in human cholangiocarcinoma tissues when compared to adjacent tissues of the same patient. Let-7c inhibited the tumorigenic properties of cholangiocarcinoma cells including their self-renewal capacity and sphere formation in vitro and subcutaneous cancer cell growth in vivo. Ectopic let-7c overexpression suppressed migration and invasion capacities of cholangiocarcinoma cell lines in vitro, however, promoted distant invasiveness in vivo. Furthermore, we found that let-7c regulated the aforementioned malignant biological properties, at least in part, through regulation of EZH2 protein expression and through the DVL3/β-catenin axis. The miRNA let-7c thus plays an important dual role in regulating tumorigenic and metastatic abilities of human cholangiocarcinoma through mechanisms involving EZH2 protein and the DVL3/β-catenin axis.