miR-509-3p promotes cisplatin-induced apoptosis in ovarian cancer cells through the regulation of anti-apoptotic genes

Pharmacogenomics. 2017 Dec;18(18):1671-1682. doi: 10.2217/pgs-2017-0115. Epub 2017 Nov 27.

Abstract

Aim: Previous observations have implicated miR-509-3p's ability in regulating cisplatin-triggered apoptosis in ovarian cancer. However, the underlying mechanisms were not fully understood.

Materials & methods: The roles of miR-509-3p in cellular apoptosis were assessed through MTT and DAPI assays. The confirmation of the regulation of BCL2 family members by miR-509-3p was investigated by luciferase reporter assay, western blot, quantitative real-time PCR and rescue experiments.

Results: MiR-509-3p can decrease the IC50 values of cisplatin and promote apoptosis in ovarian cancer cells. Furthermore, on a panel of anti-apoptotic proteins, we identified that miR-509-3p could regulate BCL2, BCL2L2 and MCL1 via their 3'UTRs.

Conclusion: Our study demonstrates that miR-509-3p could sensitize ovarian cancer cells to cisplatin treatment by targeting multiple anti-apoptosis genes including BCL2.

Keywords: BCL2; apoptosis; microRNA-509-3p; ovarian cancer.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Female
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics*
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / genetics

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • MIRN509 microRNA, human
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Cisplatin