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 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.
Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, Shaanxi, China.|Department of Pediatric Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Jiwen
J
Cheng
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.
Yanke
Y
Chen
Department of Neonatology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Pu
P
Zhao
Department of Pathology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Xi
X
Liu
Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, Shaanxi, China.
Jian
J
Dong
Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Jianhui
J
Li
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.
Chen
C
Huang
Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, Shaanxi, China.
Rongqian
R
Wu
Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi' an, Shaanxi, China.
Yi
Y
Lv
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
C572154:MIRN638 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
angiogenesis; hepatocellular carcinoma; miR-638; prognosis; vascular endothelial growth factor