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

Guohong Liu, Mingxia Yu, Balu Wu, Shuang Guo, Xin Huang, Fuling Zhou, Francois-Xavier Claret, Yunbao Pan

Research output: Contribution to journalArticle

Abstract

Jab1 overexpression correlates with poor prognosis in breast cancer patients, suggestting that targeting the aberrant Jab1 signaling in breast cancer could be a promising strategy. In the current study, we investigate the hypothesis that Jab1 positively regulates the DNA repair protein Rad51 and, in turn, the cellular response of breast cancer to chemotherapy with adriamycin and cisplatin. High-throughput mRNA sequencing (RNA-Seq) data from 113 normal and 1109 tumor tissues (obtained from TCGA) were integrated to our analysis to give further support to our findings. We found that Jab1 was overexpressed in adriamycin-resistant breast cancer cell MCF-7R compared with parental MCF-7 cells, and that knockdown of Jab1 expression conferred cellular sensitivity to adriamycin and cisplatin both in vivo and in vitro. By contrast, exogenous Jab1 expression enhanced the resistance of breast cancer cells to adriamycin and cisplatin. Moreover, we discovered that Jab1 positively regulated Rad51 in p53-dependent manner and that overexpression of Rad51 conferred cellular resistance to adriamycin and cisplatin in Jab1-deficient cells. Data from TCGA further validated an correlation between Jab1 and Rad51 in breast cancer, and elevated Jab1 and Rad51 associated with poor survival in breast cancer patients. Our findings indicate that Jab1 association with Rad51 plays an important role in cellular response to chemotherapy in breast cancer.

LanguageEnglish (US)
Pages39-48
Number of pages10
JournalCellular Signalling
Volume53
DOIs
StatePublished - Jan 1 2019

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Breast Neoplasms
Doxorubicin
Cisplatin
Drug Therapy
High-Throughput Nucleotide Sequencing
MCF-7 Cells
DNA Repair
Messenger RNA
Survival
Neoplasms
Proteins

Keywords

  • Breast cancer
  • Chemoresistance
  • Jab1/Cops5
  • Rad51

ASJC Scopus subject areas

  • Cell Biology

Cite this

Jab1/Cops5 contributes to chemoresistance in breast cancer by regulating Rad51. / Liu, Guohong; Yu, Mingxia; Wu, Balu; Guo, Shuang; Huang, Xin; Zhou, Fuling; Claret, Francois-Xavier; Pan, Yunbao.

In: Cellular Signalling, Vol. 53, 01.01.2019, p. 39-48.

Research output: Contribution to journalArticle

Liu, Guohong ; Yu, Mingxia ; Wu, Balu ; Guo, Shuang ; Huang, Xin ; Zhou, Fuling ; Claret, Francois-Xavier ; Pan, Yunbao. / Jab1/Cops5 contributes to chemoresistance in breast cancer by regulating Rad51. In: Cellular Signalling. 2019 ; Vol. 53. pp. 39-48.
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