HOTAIR maintains the stemness of ovarian cancer stem cells via the miR-206/TBX3 axis

Exp Cell Res. 2020 Oct 15;395(2):112218. doi: 10.1016/j.yexcr.2020.112218. Epub 2020 Aug 6.

Abstract

The poor prognosis of ovarian cancer is partly attributed to the frequent chemo-resistance and recurrence, which may be mediated by ovarian cancer stem cells (OCSCs). In the present study, we investigated the mechanisms contributing to the stemness of OCSCs, focusing on the long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR). Ovarian cancer cells were tested for high aldehyde dehydrogenase (ALDH) activity or high in vitro sphere-formation ability to identify OCSCs. HOTAIR was highly expressed in the OCSCs and its depletion caused a decrease in sphere-formation ability, along with reduced resistance to cisplatin and in vivo tumorigenicity. T-box transcription factor 3 (TBX3) was highly expressed in the OCSCs and was confirmed to be positively regulated by HOTAIR. Moreover, TBX3 maintained cell stemness, whereas elevating TBX3 could relieve the weakened sphere-formation ability caused by HOTAIR depletion. Subsequently, miR-206 was found to mediate the expression regulation of TBX3 by HOTAIR, and functionally involved in the regulation of stemness in OCSCs. In line with these findings, circulating HOTAIR expression was up-regulated in ovarian cancer patients. Collectively, our findings suggest that HOTAIR relieves the inhibition of TBX3 expression mediated by miR-206 in OCSCs and provide novel therapeutic targets for the treatment of ovarian cancer.

Keywords: Cancer stem cell; HOTAIR; Ovarian cancer; TBX3; miR-206.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial / drug therapy
  • Carcinoma, Ovarian Epithelial / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics
  • Neoplasm Recurrence, Local / genetics*
  • Neoplastic Stem Cells / metabolism*
  • Ovarian Neoplasms / metabolism
  • RNA, Long Noncoding / genetics*
  • T-Box Domain Proteins / drug effects
  • T-Box Domain Proteins / genetics

Substances

  • HOTAIR long untranslated RNA, human
  • MIRN206 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • T-Box Domain Proteins
  • TBX3 protein, human
  • Cisplatin