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

// Jing-Jun Yan 1, 2 , Yu-Nan Zhang 1 , Jia-Zhi Liao 1 , Kun-peng Ke 3 , Ying Chang 1 , Pei-Yuan Li 1 , Min Wang 2 , Ju-Sheng Lin 1 , Xing-Xing He 1 1 Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2 Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 3 Department 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.