MicroRNA-503 targets FGF2 and VEGFA and inhibits tumor angiogenesis and growth.
FGF2 and VEGFA are the two most potent angiogenic factors. Here we report that miR-503 can simultaneously down-regulate FGF2 and VEGFA. The expression of miR-503 is repressed in HCC cells and primary tumors due to a potential epigenetic mechanism. Overexpression of miR-503 reduced tumor angiogenesis in vitro and in vivo. We also found that miR-503 expression was down-regulated by hypoxia through HIF1α. These results identify a miRNA that targets both FGF2 and VEGFA in cancers, demonstrate the anti-angiogenesis role of miR-503 in tumorigenesis, and provide a novel mechanism for hypoxia-induced FGF2 and VEGFA through HIF1α-mediated inhibition of miR-503.
Key Laboratory of Molecular Biophysics of the Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, PR China.
Bisheng
B
Zhou
Ruihua
R
Ma
Wenxia
W
Si
Sisi
S
Li
Yan
Y
Xu
Xin
X
Tu
Qing
Q
Wang
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D020413:3' Untranslated Regions; C416003:FGF20 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C545473:MIRN503 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors