REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells

  • Authors:
    • Wenjie Wang
    • Wenjiong Sheng
    • Chenxiao Yu
    • Jianping Cao
    • Jundong Zhou
    • Jinchang Wu
    • Huojun Zhang
    • Shuyu Zhang
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  • Published online on: July 9, 2015     https://doi.org/10.3892/or.2015.4121
  • Pages: 1460-1468
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Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer. Cisplatin plays a significant role in the management of human lung cancer. Translesion DNA synthesis (TLS) is involved in DNA damage repair. DNA polymerase ζ (Pol ζ) is able to mediate the DNA replication bypass of DNA damage, which is suggested to be involved in chemoresistance. REV3L is the catalytic subunit of Pol ζ. Due to its critical role in translesion DNA synthesis, whether REV3L modulates cisplatin response in NSCLC cells remains unknown. In this study, REV3L overexpression and silencing H1299 cell lines were established. The reports showed that cisplatin induced the expression of REV3L by recruiting Sp1 to its promoter. Similar results were obtained when the ability of the cells to express luciferase from a platinated plasmid was measured. Co-transfection of the reporter with the REV3L overexpression vector or REV3L plus REV7L significantly enhanced the reporter activity. Nuclear condensation and fragmentation of shRNA-REV3L H1299 cells were more pronounced than shRNA-NC H1299 cells after cisplatin exposure, indicating that REV3L overexpression abolished cisplatin-induced DNA damage. Moreover, a forced expression of REV3L conferred the resistance of H1299 cells to cisplatin, whereas the knockdown of REV3L sensitized cisplatin efficacy in H1299 cells. Taken together, we demonstrated that inhibition of REV3L sensitized lung cancer H1299 cells to cisplatin treatment. Thus, REV3L may be a novel target for the chemotherapy of NSCLC.
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September-2015
Volume 34 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wang W, Sheng W, Yu C, Cao J, Zhou J, Wu J, Zhang H and Zhang S: REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells. Oncol Rep 34: 1460-1468, 2015
APA
Wang, W., Sheng, W., Yu, C., Cao, J., Zhou, J., Wu, J. ... Zhang, S. (2015). REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells. Oncology Reports, 34, 1460-1468. https://doi.org/10.3892/or.2015.4121
MLA
Wang, W., Sheng, W., Yu, C., Cao, J., Zhou, J., Wu, J., Zhang, H., Zhang, S."REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells". Oncology Reports 34.3 (2015): 1460-1468.
Chicago
Wang, W., Sheng, W., Yu, C., Cao, J., Zhou, J., Wu, J., Zhang, H., Zhang, S."REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells". Oncology Reports 34, no. 3 (2015): 1460-1468. https://doi.org/10.3892/or.2015.4121