High expression of RAD51 promotes DNA damage repair and survival in KRAS-mutant lung cancer cells

BMB Rep. 2019 Feb;52(2):151-156. doi: 10.5483/BMBRep.2019.52.2.213.

Abstract

RAD51 recombinase plays a critical role in homologous recombination and DNA damage repair. Here we showed that expression of RAD51 is frequently upregulated in lung cancer tumors compared with normal tissues and is associated with poor survival (hazard ratio (HR) = 2, P = 0.0009). Systematic investigation of lung cancer cell lines revealed higher expression of RAD51 in KRAS mutant (MT) cells compared to wildtype (WT) cells. We further showed that MT KRAS, but not WT KRAS, played a critical role in RAD51 overexpression via MYC. Moreover, our results revealed that KRAS MT cells are highly dependent on RAD51 for survival and depletion of RAD51 resulted in enhanced DNA double strand breaks, defective colony formation and cell death. Together, our results suggest that mutant KRAS promotes RAD51 expression to enhance DNA damage repair and lung cancer cell survival, suggesting that RAD51 may be an effective therapeutic target to overcome chemo/radioresistance in KRAS mutant cancers. [BMB Reports 2019; 52(2): 151-156].

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / physiology
  • DNA Breaks, Double-Stranded
  • DNA Damage*
  • DNA Repair*
  • Homologous Recombination
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Rad51 Recombinase / biosynthesis*
  • Rad51 Recombinase / genetics
  • Up-Regulation

Substances

  • KRAS protein, human
  • RAD51 protein, human
  • Rad51 Recombinase
  • Proto-Oncogene Proteins p21(ras)