Long non-coding RNA THOR promotes cell proliferation and metastasis in hepatocellular carcinoma

Gene. 2018 Dec 15:678:129-136. doi: 10.1016/j.gene.2018.08.035. Epub 2018 Aug 8.

Abstract

Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the development and progression of multiple cancers by previous studies. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in hepatocellular carcinoma (HCC) is still unclear. In this study, we found that THOR was relatively highly expressed in human HCC tissues and cell lines. Notably, high THOR expression was associated with worse prognosis. THOR depletion resulted in significant inhibition of the growth and metastasis of HCC cells. Mechanistically, THOR drives HCC cell progression via the PTEN/AKT pathway. Moreover, the specific PI3-K inhibitor LY294002 abolished the discrepancy in the growth and metastatic capacity between THOR-silenced HCC cells and control cells, which further confirmed that AKT was required in THOR-driven HCC cell growth and metastasis. Taken together, our results suggest that THOR could promote HCC cell growth and metastasis by amplifying PTEN/AKT signaling and may be a new therapeutic target and predictive factor for HCC.

Keywords: AKT; Hepatocellular carcinoma; Metastasis; Proliferation; THOR.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • PTEN Phosphohydrolase / genetics
  • Prognosis
  • Proto-Oncogene Proteins c-akt / genetics
  • RNA, Long Noncoding / genetics*
  • Signal Transduction
  • Up-Regulation*

Substances

  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human