MiR-199a/b-5p inhibits hepatocellular carcinoma progression by post-transcriptionally suppressing ROCK1

// Yangyang Zhan 1, * , NanXin Zheng 2, * , Fei Teng 2, * , Leilei Bao 1, 3 , Fang Liu 2 , Mingjian Zhang 1 , Meng Guo 1, 2 , Wenyuan Guo 2 , Guoshan Ding 2 and Quanxing Wang 1 1 Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China 2 Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China 3 Department of Pharmacy, No. 411 Hospital of PLA, Shanghai 200080, China * These authors have contributed equally to this work Correspondence to: Quanxing Wang, email: wangqx@immunol.org Guoshan Ding, email: dingguoshanmail@163.com Keywords: miRNA, hepatocellular carcinoma, miR-199a/b-5p, metastasis, ROCK1 Received: January 20, 2017 Accepted: April 26, 2017 Published: May 22, 2017 ABSTRACT In this study, we explored the actions of miR-199a/b-5p during hepatocellular carcinoma (HCC) progression and its potential target genes. Through heatmap miRNA expression analysis of 15 matched HCC tumor and adjacent non-tumor liver tissues from the TCGA database, we detected 19 mRNAs that were upregulated and 13 that were downregulated specifically in HCC. Among these, miR-199 family members were downregulated in HCC tumors and cell lines, as compared to controls. Low miR-199a/b-5p expression was also associated with poor overall survival of HCC patients. miR-199a/b-5p overexpression in HCC cell lines inhibited cell proliferation, migration and invasion, both in vitro and in vivo . In addition, miR199-a/b-5p post-transcriptionally suppressed Rho-associated coiled-coil kinase 1 (ROCK1). This in turn led to inhibition of ROCK1/MLC and PI3K/Akt signaling, which is necessary for HCC proliferation and metastasis. These results indicate that miR-199a/b acts as tumor suppressors in HCC and represent promising therapeutic targets.