Oncotarget

Research Papers:

Methylation-regulated miR-124-1 suppresses tumorigenesis in hepatocellular carcinoma by targeting CASC3

Ling Xu, Weiqi Dai, JingJing Li, Lei He, Fan Wang, Yujing Xia, Kan Chen, Sainan Li, Tong Liu, Jie Lu, Yingqun Zhou, Yugang Wang _ and Chuanyong Guo

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Oncotarget. 2016; 7:26027-26041. https://doi.org/10.18632/oncotarget.8266

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Abstract

Ling Xu1,2,*, Weiqi Dai1,*, JingJing Li1,*, Lei He1,*, Fan Wang1, Yujing Xia1, Kan Chen1, Sainan Li1, Tong Liu1, Jie Lu1, Yingqun Zhou1, Yugang Wang2, Chuanyong Guo1

1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China

2Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China

*These authors contributed equally to this work

Correspondence to:

Ling Xu, e-mail: [email protected]

Chuan-Yong Guo, e-mail: [email protected]

Keywords: miR-124-1, hepatocellular carcinoma, methylation, CASC3

Received: October 10, 2015     Accepted: March 08, 2016     Published: March 22, 2016

ABSTRACT

This study was to investigate the roles and mechanisms of miR-124-1 in hepatocellular carcinoma (HCC). We analyzed the expression of miR-124-1 in human HCC tissues and cell lines. Luciferase reporter assays were used to analyze the target of miR-124-1. Human HCC cell lines were transduced with lentiviruses expressing miR-124-1, and proliferation and colony formation were analyzed. The growth of human HCC cells overexpressing miR-124-1 was assessed in nude mice. The expression of p38-MAPK, JNK, ERK and related signaling molecules was detected by western blotting and immunohistochemistry. Our results showed that miR-124-1 levels were reduced in HCC tissues and cell lines compared with those in adjacent non-cancer tissues and normal liver cell lines respectively. Downregulation of miR-124-1 in HCC cell lines were attributed to hypermethylation of its promoter region. Overexpression of miR-124-1 inhibited HCC cell proliferation in vitro, whereas miR-124-1 was correlated with clinicopathological parameters of HCC patients. HCC cell-mediated overexpression of miR-124-1 in nude mice suppressed tumor growth. Cancer susceptibility candidate 3 (CASC3) was identified as a direct target of miR-124-1 by computational analysis and experimental assays. MiR-124-1-mediated downregulation of CASC3 resulted in the inactivation of p38-MAPK, JNK and ERK. Our findings provide potential new targets for the prevention or treatment of HCC.


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