ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells

Lingjie Bao, Jianfa Wu, Matthew Dodson, Elisa Montserrat Rojo de la Vega, Yan Ning, Zhenbo Zhang, Ming Yao, Donna D. Zhang, Congjian Xu, Xiaofang Yi

Research output: Research - peer-reviewArticle

  • 4 Citations

Abstract

Previously, we have demonstrated that NRF2 plays a key role in mediating cisplatin resistance in ovarian cancer. To further explore the mechanism underlying NRF2-dependent cisplatin resistance, we stably overexpressed or knocked down NRF2 in parental and cisplatin-resistant human ovarian cancer cells, respectively. These two pairs of stable cell lines were then subjected to microarray analysis, where we identified 18 putative NRF2 target genes. Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters, has previously been reported to contribute to chemoresistance in clear cell ovarian cancer. A detailed analysis on ABCF2 revealed a functional antioxidant response element (ARE) in its promoter region, establishing ABCF2 as an NRF2 target gene. Next, we investigated the contribution of ABCF2 in NRF2-mediated cisplatin resistance using our stable ovarian cancer cell lines. The NRF2-overexpressing cell line, containing high levels of ABCF2, was more resistant to cisplatin-induced apoptosis compared to its control cell line; whereas the NRF2 knockdown cell line with low levels of ABCF2, was more sensitive to cisplatin treatment than its control cell line. Furthermore, transient overexpression of ABCF2 in the parental cells decreased apoptosis and increased cell viability following cisplatin treatment. Conversely, knockdown of ABCF2 using specific siRNA notably increased apoptosis and decreased cell viability in cisplatin-resistant cells treated with cisplatin. This data indicate that the novel NRF2 target gene, ABCF2, plays a critical role in cisplatin resistance in ovarian cancer, and that targeting ABCF2 may be a new strategy to improve chemotherapeutic efficiency.

LanguageEnglish (US)
Pages1543-1553
Number of pages11
JournalMolecular Carcinogenesis
Volume56
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Ovarian Neoplasms
Cisplatin
Genes
Cell Line
Apoptosis
Cell Survival
Antioxidant Response Elements
ATP-Binding Cassette Transporters
Microarray Analysis
Genetic Promoter Regions
Small Interfering RNA

Keywords

  • ABCF2
  • chemoresistance
  • cisplatin
  • NRF2
  • ovarian cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Bao, L., Wu, J., Dodson, M., Rojo de la Vega, E. M., Ning, Y., Zhang, Z., ... Yi, X. (2017). ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells. Molecular Carcinogenesis, 56(6), 1543-1553. DOI: 10.1002/mc.22615

ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells. / Bao, Lingjie; Wu, Jianfa; Dodson, Matthew; Rojo de la Vega, Elisa Montserrat; Ning, Yan; Zhang, Zhenbo; Yao, Ming; Zhang, Donna D.; Xu, Congjian; Yi, Xiaofang.

In: Molecular Carcinogenesis, Vol. 56, No. 6, 01.06.2017, p. 1543-1553.

Research output: Research - peer-reviewArticle

Bao, L, Wu, J, Dodson, M, Rojo de la Vega, EM, Ning, Y, Zhang, Z, Yao, M, Zhang, DD, Xu, C & Yi, X 2017, 'ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells' Molecular Carcinogenesis, vol 56, no. 6, pp. 1543-1553. DOI: 10.1002/mc.22615
Bao L, Wu J, Dodson M, Rojo de la Vega EM, Ning Y, Zhang Z et al. ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells. Molecular Carcinogenesis. 2017 Jun 1;56(6):1543-1553. Available from, DOI: 10.1002/mc.22615
Bao, Lingjie ; Wu, Jianfa ; Dodson, Matthew ; Rojo de la Vega, Elisa Montserrat ; Ning, Yan ; Zhang, Zhenbo ; Yao, Ming ; Zhang, Donna D. ; Xu, Congjian ; Yi, Xiaofang. / ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells. In: Molecular Carcinogenesis. 2017 ; Vol. 56, No. 6. pp. 1543-1553
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