LncRNA OR3A4 participates in the angiogenesis of hepatocellular carcinoma through modulating AGGF1/akt/mTOR pathway

Eur J Pharmacol. 2019 Apr 15:849:106-114. doi: 10.1016/j.ejphar.2019.01.049. Epub 2019 Jan 30.

Abstract

Hepatocellular carcinoma (HCC), as the commonest type in liver cancer, is in urgent need for better treatment target due to its high mortality and poor prognosis. The involvement of angiogenesis in HCC has been identified by multiple studies, but the underlying mechanism remains unclear. Long non-coding RNAs (LncRNAs) have been reported to regulate numerous cancers, including HCC. LncRNA-OR3A4 has been reported to exert oncogenic and angiogenetic functions in gastric cancer, but its role in HCC hasn't been elucidated. Present study aimed to uncover the biological role of OR3A4 in tumor progression and angiogenesis in HCC. The upregulation of OR3A4 in HCC tissues and cell lines and its prognostic significance were first identified. Loss-of-function assays, including CCK-8, transwell and tube formation assay, validated OR3A4 as a promoter for HCC progression and angiogenesis. The association of OR3A4 and AGGF1 with HCC and poor prognosis was identified by qRT-PCR and Kaplan-Meier analysis. Western blotting and spearman's correlation curve verified the effect of OR3A4 on AGGF1 level and their positive association. Rescue assays revealed that OR3A4 promoted cancer progression and angiogenesis in HCC via AGGF1/akt/mTOR. Together, present study revealed OR3A4 as a novel prognostic target for HCC, which regulated tumor progression and angiogenesis through AGGF1/akt/mTOR pathway.

Keywords: AGGF1; Angiogenesis; HCC; OR3A4; akt; mTOR.

MeSH terms

  • Angiogenic Proteins / genetics
  • Angiogenic Proteins / metabolism*
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / genetics*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Long Noncoding / genetics*
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation

Substances

  • AGGF1 protein, human
  • Angiogenic Proteins
  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases