J Cancer 2017; 8(4):617-625. doi:10.7150/jca.17394

Research Paper

MicroRNA-200a inhibits cell growth and metastasis by targeting Foxa2 in hepatocellular carcinoma

Shu-ying Chen1*, De-ning Ma2*, Qiu-dan Chen3*, Jing-jun Zhang1, Yue-ru Tian1, Zhi-cheng Wang1, Hao Cai4, Yong Lin1✉, Hui-chuan Sun4✉

1. Huashan Hospital, Fudan University, 12 Wulumuqi middle Road, Shanghai 200040, People's Republic of China
2. Department of Liver Surgery, Fudan University, Shanghai Cancer Center, Cancer Hospital, 270 Dongan Road, Shanghai, People's Republic of China
3. Department of Central Laboratory, Clinical Laboratory, Jingan District Central Hospital, Fudan University, 259 Xikang Road, Shanghai20040, People's Republic of China
4. Liver Cancer Institute, Zhongshan Hospital, Fudan University,1609 Xietu Road, Shanghai 200032, People's Republic of China
*Contributed equally.

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Chen Sy, Ma Dn, Chen Qd, Zhang Jj, Tian Yr, Wang Zc, Cai H, Lin Y, Sun Hc. MicroRNA-200a inhibits cell growth and metastasis by targeting Foxa2 in hepatocellular carcinoma. J Cancer 2017; 8(4):617-625. doi:10.7150/jca.17394. Available from http://www.jcancer.org/v08p0617.htm

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Background: MicroRNAs (miRNAs) are a class of endogenous, small non-coding RNAs which function as essential posttranscriptional modulators of gene expression tightly involved in a wide range of diseases, including the hepatocellular carcinoma (HCC). Here, the present study was designed to investigate the expression levels and cellular roles of miR-200a in HCC.

Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-200a in serums and cell lines. Bioinformation analysis, the luciferase reporter assay, qRT-PCR and western blotting were employed to validate Foxa2 as a direct target gene of miR-200a. Cell proliferation, migration and invasion were assessed to identify whether miR-200a could regulate the biological behaviors of HCC cells by targeting Foxa2.

Results: In this study, a low level of miR-200a was observed in patients' serums and HCC cell lines. Overexpression of miR-200a in HCC cell lines reduced cell proliferation, migration and invasion. In addition, transcription factor forkhead box A2 (Foxa2) was identified as a novel target of miR-200a and downregulated at mRNA and protein levels in miR-200a overexpressed cells. Meanwhile, restoration of Foxa2 significantly reversed the tumor suppressive effects of miR-200a.

Conclusions: These findings indicate that miR-200a regulates the proliferation, migration and invasion of HCC cells by targeting Foxa2, suggesting that miR-200a may function as a potential therapeutic molecular for the diagnosis and treatment of the liver cancer.

Keywords: miR-200a, Foxa2, hepatocellular carcinoma, proliferation, migration, invasion.