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

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 tha...

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Bibliographic Details
Published in:Oncotarget 2016-05, Vol.7 (21), p.30702-30711
Main Authors: Cheng, Jiwen, Chen, Yanke, Zhao, Pu, Liu, Xi, Dong, Jian, Li, Jianhui, Huang, Chen, Wu, Rongqian, Lv, Yi
Format: Article
Language:English
Subjects:
Animals
Carcinogenesis - genetics
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs - metabolism
Middle Aged
Neovascularization, Pathologic - genetics
Research Paper
Signal Transduction - genetics
Vascular Endothelial Growth Factor A - genetics
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.8930