Oncotarget

Research Papers:

MiR-497 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting VEGFA and AEG-1

Jing-Jun Yan, Yu-Nan Zhang, Jia-Zhi Liao, Kun-peng Ke, Ying Chang, Pei-Yuan Li, Min Wang, Ju-Sheng Lin and Xing-Xing He _

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Oncotarget. 2015; 6:29527-29542. https://doi.org/10.18632/oncotarget.5012

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Abstract

Jing-Jun Yan1,2, Yu-Nan Zhang1, Jia-Zhi Liao1, Kun-peng Ke3, Ying Chang1, Pei-Yuan Li1, Min Wang2, Ju-Sheng Lin1, Xing-Xing He1

1Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

2Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

3Department of Cardiac Surgery, Wuhan Asia Heart Hospital, Wuhan 430022, China

Correspondence to:

Xing-Xing He, e-mail: xxhe@tjh.tjmu.edu.cn

Keywords: hepatocellular carcinoma, microRNA, tumor biology, cancer

Received: April 01, 2015     Accepted: August 10, 2015     Published: August 21, 2015

ABSTRACT

Hepatocellular carcinoma (HCC) is a worldwide malignance and displays marked vascular abnormalities and active metastasis. MicroRNAs (miRNAs) have been shown to play important roles in regulating tumor properties in cancer, however, whether miR-497 contributes to HCC angiogenesis or metastasis remains unclear. In this study, we found that miR-497 was significantly down-regulated in HCC tissue samples and cell lines. Gain-of-function and loss-of-function studies revealed that miR-497 could repress both the pro-angiogenic and metastatic ability of HCC cells. Subsequent investigations disclosed that miR-497 directly inhibited the 3′-untranslated regions (UTRs) of vascular endothelial growth factor A (VEGFA) and astrocyte elevated gene-1 (AEG-1). Furthermore, overexpression of these targets antagonized the function of miR-497. Based on nude mouse models, we demonstrated that overexpression of miR-497 significantly repressed microvessel densities in xenograft tumors and reduced pulmonary metastasis. In conclusion, our findings indicate that miR-497 downregulation contributes to angiogenesis and metastasis in HCC.


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