Oncotarget

Research Papers:

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

Jiwen Cheng, Yanke Chen, Pu Zhao, Xi Liu, Jian Dong, Jianhui Li, Chen Huang, Rongqian Wu and Yi Lv _

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Oncotarget. 2016; 7:30702-30711. https://doi.org/10.18632/oncotarget.8930

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Abstract

Jiwen Cheng1,2,*, Yanke Chen3,*, Pu Zhao4, Xi Liu5, Jian Dong1, Jianhui Li6, Chen Huang3, Rongqian Wu1, Yi Lv1

1Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’ an, Shaanxi, China

2Department of Pediatric Surgery, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China

3Department 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

4Department of Neonatology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China

5Department of Pathology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China

6Department of Surgical Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China

*These authors contributed equally to this work

Correspondence to:

Rongqian Wu, email: [email protected]

Yi Lv, email: [email protected]

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.


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