Int J Biol Sci 2019; 15(8):1591-1599. doi:10.7150/ijbs.34113

Research Paper

miR-424-5p represses the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5

Jingbang Wu1,2,3,4*, Beng Yang1,2,3,4*, Yanpeng Zhang1,2,3,4, Xiaode Feng1,2,3,4, Bin He1,2,3,4, Haiyang Xie1,2,3,4, Lin Zhou1,2,3,4, Jian Wu1,2,3,4, Shusen Zheng1,2,3,4✉

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.

Abstract

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

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How to cite this article:
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