MicroRNA-210 promotes cancer angiogenesis by targeting fibroblast growth factor receptor-like 1 in hepatocellular carcinoma.
Hypoxia drives cancer to become more aggressive, particularly angiogenesis, and the corresponding mechanisms still need to be further investigated. In hepatocellular carcinoma (HCC), the master hypoxia-induced microRNA (miRNA) miR-210 is upregulated in HCC and participates in HCC progression, but its roles in hypoxia-induced HCC angiogenesis are still unknown. Moreover, the correlation between miR-210 expression and HCC clinical progression also needs elucidation. In the present study, we found that miR-210 expression was progressively increased from normal liver and adjacent non-tumor tissues, to incipient and advanced tumor tissues. In HCC patients, high miR-210 expression was significantly correlated with poor prognosis, both tumor-free survival and overall survival. Moreover, miR-210 expression in HCC was significantly positively correlated with microvascular density. Both in vitro and in vivo studies determined that miR-210 promoted HCC angiogenesis, and the corresponding mechanism was identified to be the direct targeting and inhibition of fibroblast growth factor receptor-like 1 (FGFRL1) expression. Thus, we suggest a new prognosis predictor for HCC patients, and determined the roles of hypoxic miR-210 in HCC angiogenesis.
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Yun
Y
Yang
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Jin
J
Zhang
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Tian
T
Xia
The Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Gaiyun
G
Li
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Tao
T
Tian
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Mengchao
M
Wang
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Ruoyu
R
Wang
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Linghao
L
Zhao
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Yuan
Y
Yang
The Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Ke
K
Lan
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China.
Weiping
W
Zhou
D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D051500:Receptor, Fibroblast Growth Factor, Type 5 / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
C417531:FGFRL1 protein, human; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D051500:Receptor, Fibroblast Growth Factor, Type 5