MiR-199a/b-5p inhibits hepatocellular carcinoma progression by post-transcriptionally suppressing ROCK1
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Yangyang Zhan1,*, NanXin Zheng2,*, Fei Teng2,*, Leilei Bao1,3, Fang Liu2, Mingjian Zhang1, Meng Guo1,2, Wenyuan Guo2, Guoshan Ding2 and Quanxing Wang1
1Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China
2Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
3Department of Pharmacy, No. 411 Hospital of PLA, Shanghai 200080, China
*These authors have contributed equally to this work
Quanxing Wang, email: [email protected]
Guoshan Ding, email: [email protected]
Keywords: miRNA, hepatocellular carcinoma, miR-199a/b-5p, metastasis, ROCK1
Received: January 20, 2017 Accepted: April 26, 2017 Published: May 22, 2017
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.
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