Downregulation of miRNA-638 promotes angiogenesis and growth of hepatocellular carcinoma by targeting VEGF.

// Jiwen Cheng 1, 2, * , Yanke Chen 3, * , Pu Zhao 4 , Xi Liu 5 , Jian Dong 1 , Jianhui Li 6 , Chen Huang 3 , Rongqian Wu 1 , Yi Lv 1 1 Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’ an, Shaanxi, China 2 Department of Pediatric Surgery, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China 3 Department of Genetics and Cell Biology, Environment and Genes Related to Diseases Key Laboratory of Education Ministry, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, China 4 Department of Neonatology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China 5 Department of Pathology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China 6 Department of Surgical Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China * These authors contributed equally to this work Correspondence to: Rongqian Wu, email: wurq@yahoo.com Yi Lv, email: luyi1698@126.com Keywords: hepatocellular carcinoma, miR-638, vascular endothelial growth factor, angiogenesis, prognosis Received: February 01, 2016      Accepted: April 02, 2016      Published: April 22, 2016 ABSTRACT The expression and function of microRNA-638 (miR-638) in hepatocellular carcinoma (HCC) remained unknown. Using the miRNA target prediction tools, we predicted that the vascular endothelial growth factor (VEGF) might be a direct target of miR-638. The aim of this study was to test the hypothesis that downregulation of miRNA-638 promotes angiogenesis and growth of HCC by targeting the VEGF signaling pathway. We found that miR-638 was significantly downregulated in HCC cells and clinical HCC specimens, and miR-638 levels were inversely correlated with tumor size, portal vein invasion and poor prognosis. Overexpression of miR-638 inhibited the processes of tumor angiogenesis in vitro and in vivo . The xenograft mouse model experiments showed miR-638 repressed tumor growth of HCC in vivo . Using a luciferase reporter assay, we identified VEGF as a direct target of miR-638. Subsequent investigation revealed that miR-638 expression was inversely correlated with VEGF expression in human HCC samples. Taken together, these results suggested that miR-638 is a novel therapeutic target for HCC and overexpression of miR-638 could suppress angiogenesis and tumor growth of HCC by inhibiting VEGF signaling.