Long non-coding RNA DUXAP9 promotes hepatocellular carcinoma cell stemness via directly interacting with sox9

Environ Toxicol. 2021 Sep;36(9):1793-1801. doi: 10.1002/tox.23300. Epub 2021 Jun 4.

Abstract

Long non-coding RNA (LncRNA) DUXAP9 expression was recently found to be higher in hepatocellular carcinoma (HCC) tissues and cells, and correlated with a shorter overall survival of HCC patients. However, its roles in HCC progression have never been revealed. Here, the roles of DUXAP9 in HCC cell stemness are explored as cancer stem cells (CSCs) contribute to one of the root of cancer progression. We found that DUXAP9 positively regulated HCC cell stemness, as characterized by the change of sphere-formation ability, ALDH activity and stemness marker expression. Further luciferase reporter, mRNA stability and RNA-RNA in vitro interaction assays indicated that DUXAP9 directly bound to the 3' untranslated region (UTR) of sox9, enhanced the mRNA stability of sox9 and thus increased sox9 expression. Notably, the effects induced by DUXAP9 on HCC cell stemness depended on sox9 expression. Therefore, this work identifies a novel DUXAP9/sox9 axis essential for HCC cell stemness.

Keywords: DUXAP9; Sox9; hepatocellular carcinoma; long non-coding RNA; stemness.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / genetics
  • MicroRNAs*
  • Neoplastic Stem Cells*
  • RNA, Long Noncoding* / genetics
  • SOX9 Transcription Factor* / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • SOX9 Transcription Factor
  • SOX9 protein, human