Int J Biol Sci 2019; 15(8):1591-1599. doi:10.7150/ijbs.34113
miR-424-5p represses the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5
1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, School of Medicine, Zhejiang University
2. NHC Key Laboratory of Combined Multi-organ Transplantation
3. Key Laboratory of the diagnosis and treatment of organ Transplantation,CAMS
4. Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 310003,China
*These authors contributed equally to this work.
Wu J, Yang B, Zhang Y, Feng X, He B, Xie H, Zhou L, Wu J, Zheng S. miR-424-5p represses the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5. Int J Biol Sci 2019; 15(8):1591-1599. doi:10.7150/ijbs.34113. Available from http://www.ijbs.com/v15p1591.htm
MicroRNAs (miRNAs) have been validated to play prominent roles in the occurrence and development of many kinds of malignant cancer. MiR-424-5p has been reported to participate in various tumors proliferation and metastasis as a suppressor. On the contrary, miR-424-5p would promote cell proliferation in some tumors. However, the expression of miR-424-5p in intrahepatic cholangiocarcinoma (ICC) is rarely reported and its mechanism remains unclear. Here, we discover that miR-424-5p is frequently downregulated in ICC tissues compared with adjacent normal tissues and in ICC cells. Over-expression of miR-424-5p significantly inhibits the invasion and migration of ICC cells in vitro. Importantly, miR-424-5p is found to be a suppressor of ARK5, by binding to 3'-UTR of ARK5 mRNA and then inhibiting mTOR phosphorylated, thus deregulating epithelial-mesenchymal transition (EMT) of ICC. Furthermore, ARK5 is found to play a role in ICC metastasis and regulating EMT. Knockdown of ARK5 inhibits invasion and migration of ICC, while the over-expression gives an opposite effect. Besides, high-expression of ARK5 is also associated with poor prognosis. In conclusion, our study reveals that miR-424-5p is critical to the invasion, migration and EMT progression in ICC cells. Targeting the pathway described here may be a novel approach to inhibit metastasis of ICC and the restoration of miR-424-5p expression may be a promising strategy for ICC therapy.
Keywords: intrahepatic cholangiocarcinoma (ICC), miR-424-5p, ARK5, EMT, mTOR