Suppression of DDX39B sensitizes ovarian cancer cells to DNA-damaging chemotherapeutic agents via destabilizing BRCA1 mRNA

Oncogene. 2020 Nov;39(47):7051-7062. doi: 10.1038/s41388-020-01482-x. Epub 2020 Sep 28.


Multiple RNA processing events including transcription, mRNA splicing, and export are delicately coordinated by the TREX complex. As one of the essential subunits, DDX39B couples the splicing and export machineries by recruiting ALYREF onto mRNA. In this study, we further explore the functions of DDX39B in handling damaged DNA, and unexpectedly find that DDX39B facilitates DNA repair by homologous recombination through upregulating BRCA1. Specifically, DDX39B binds to and stabilizes BRCA1 mRNA. DDX39B ensures ssDNA formation and RAD51 accumulation at DSB sites by maintaining BRCA1 levels. Without DDX39B being present, ovarian cancer cells exhibit hypersensitivity to DNA-damaging chemotherapeutic agents like platinum or PARPi. Moreover, DDX39B-deficient mice show embryonic lethality or developmental retardation, highly reminiscent of those lacking BRCA1. High DDX39B expression is correlated with worse survival in ovarian cancer patients. Thus, DDX39B suppression represents a rational approach for enhancing the efficacy of chemotherapy in BRCA1-proficient ovarian cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Cell Line, Tumor
  • DEAD-box RNA Helicases / antagonists & inhibitors
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • DNA Breaks, Double-Stranded / drug effects
  • DNA, Single-Stranded / metabolism
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • RNA Splicing / drug effects
  • RNA Stability / drug effects
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Rad51 Recombinase / metabolism
  • Recombinational DNA Repair / drug effects
  • Survival Rate
  • Transcription Factors / metabolism
  • Up-Regulation


  • ALYREF protein, human
  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • DNA, Single-Stranded
  • Nuclear Proteins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • RNA, Messenger
  • RNA-Binding Proteins
  • Transcription Factors
  • Ddx39b protein, mouse
  • RAD51 protein, human
  • Rad51 Recombinase
  • DDX39B protein, human
  • DEAD-box RNA Helicases