MicroRNA-210 promotes cancer angiogenesis by targeting fibroblast growth factor receptor-like 1 in hepatocellular carcinoma

Oncol Rep. 2016 Nov;36(5):2553-2562. doi: 10.3892/or.2016.5129. Epub 2016 Sep 23.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • Receptor, Fibroblast Growth Factor, Type 5 / biosynthesis*
  • Receptor, Fibroblast Growth Factor, Type 5 / genetics
  • Xenograft Model Antitumor Assays

Substances

  • FGFRL1 protein, human
  • MIRN210 microRNA, human
  • MicroRNAs
  • Receptor, Fibroblast Growth Factor, Type 5