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.