Open AccessDownregulation of miRNA-638 promotes angiogenesis and growth of hepatocellular carcinoma by targeting VEGF
Author(s) -
Jiwen Cheng,
Yanke Chen,
Pengwei Zhao,
Xi Liu,
Jian Dong,
Jianhui Li,
Chen Huang,
Rongqian Wu,
Yi Lv
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.8930
Subject(s) - downregulation and upregulation , hepatocellular carcinoma , angiogenesis , cancer research , microrna , medicine , vegf receptors , vascular endothelial growth factor a , vascular endothelial growth factor , oncology , biology , gene , biochemistry
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.