YY1-Induced lncRNA PART1 Enhanced Resistance of Ovarian Cancer Cells to Cisplatin by Regulating miR-512-3p/CHRAC1 Axis

DNA Cell Biol. 2021 Jun;40(6):821-832. doi: 10.1089/dna.2021.0059. Epub 2021 May 24.

Abstract

Chemoresistance is one of the major obstacles encountered in ovarian cancer (OC) therapy. Long noncoding RNA PART1 has been reported to be involved in the tumorigenesis of several types of cancers. However, the biological role of PART1 in the chemoresistance of OC is still unclear. In this study, it was found that the expression levels of PART1 and CHRAC1 were increased and miR-512-3p expression was decreased in cisplatin (DDP)-resistant OC cell lines. The depletion of PART1 enhanced the DDP sensitivity of DDP-resistant OC cells, as indicated by the inhibition of cell proliferation, migration, and invasion, and promotion of cell apoptosis. In the upstream mechanism exploration, we discovered that PART1 was induced by YY1 transcription factor. Moreover, it was identified that miR-512-3p was a target of PART1, and PART1 regulated the DDP resistance of OC through miR-512-3p. In addition, we screened the candidate genes of miR-512-3p., and confirmed that CHRAC1 was the downstream gene of miR-512-3p. Furthermore, the knockdown of CHRAC1 inhibited proliferation, migration, and invasion, and accelerated apoptosis of DDP-resistant OC cells, which was counteracted after the inhibition of miR-512-3p. Finally, we observed that PART1 regulated the expression of CHRAC1 through miR-512-3p. In conclusion, we demonstrated that YY1-induced PART1 accelerated DDP resistance of OC through miR-512-3p/CHRAC1 axis, suggesting PART1 may be a promising therapeutic target for DDP-resistant OC patients.

Keywords: CHRAC1; OC; PART1; miR-512-3p; resistance.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • DNA-Binding Proteins / metabolism*
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / metabolism*
  • Nucleoproteins / metabolism*
  • Ovarian Neoplasms / metabolism*
  • RNA, Untranslated / physiology*
  • YY1 Transcription Factor / physiology*

Substances

  • CHRAC1 protein, human
  • DNA-Binding Proteins
  • MIRN512 microRNA, human
  • MicroRNAs
  • Nucleoproteins
  • PART-1 RNA, human
  • RNA, Untranslated
  • YY1 Transcription Factor
  • YY1 protein, human
  • Cisplatin