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Oncotarget. 2016 May 24;7(21):30702-11. doi: 10.18632/oncotarget.8930.

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

Author information

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.

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.

KEYWORDS:

angiogenesis; hepatocellular carcinoma; miR-638; prognosis; vascular endothelial growth factor

PMID:
27120793
PMCID:
PMC5058711
DOI:
10.18632/oncotarget.8930
[Indexed for MEDLINE]
Free PMC Article

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