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Jab1/Cops5 contributes to chemoresistance in breast cancer by regulating Rad51

Guohong Liu1, Mingxia Yu2, Balu Wu3

  • 1Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.

Cellular Signalling
|September 24, 2018
PubMed

Insights

Targeting Jab1 (Jun activation domain-binding protein 1) could improve breast cancer chemotherapy. Jab1 promotes DNA repair protein Rad51, enhancing resistance to adriamycin and cisplatin, and is linked to poor patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Jab1 overexpression is linked to poor prognosis in breast cancer.
  • Targeting Jab1 signaling presents a potential therapeutic strategy for breast cancer.

Purpose of the Study:

  • To investigate the role of Jab1 in regulating the DNA repair protein Rad51.
  • To determine the impact of Jab1 on breast cancer response to chemotherapy drugs adriamycin and cisplatin.

Main Methods:

  • Utilized high-throughput mRNA sequencing (RNA-Seq) data from The Cancer Genome Atlas (TCGA).
  • Compared Jab1 expression in adriamycin-resistant vs. parental breast cancer cells (MCF-7R vs. MCF-7).
  • Assessed the effects of Jab1 knockdown and overexpression on cellular sensitivity to chemotherapy in vitro and in vivo.

Main Results:

  • Jab1 was overexpressed in adriamycin-resistant MCF-7R cells.
  • Knockdown of Jab1 increased sensitivity to adriamycin and cisplatin.
  • Exogenous Jab1 expression enhanced chemoresistance.
  • Jab1 positively regulated Rad51 in a p53-dependent manner.
  • Rad51 overexpression conferred chemoresistance in Jab1-deficient cells.
  • TCGA data confirmed a correlation between Jab1 and Rad51, associated with poor patient survival.

Conclusions:

  • Jab1 positively regulates Rad51, influencing breast cancer cell response to chemotherapy.
  • The Jab1-Rad51 association is a critical factor in chemotherapy resistance in breast cancer.
  • Targeting Jab1 may represent a viable strategy to overcome chemoresistance in breast cancer patients.
Keywords:
Breast cancerChemoresistanceJab1/Cops5Rad51

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