SIRT1 downregulation enhances chemosensitivity and survival of adult T-cell leukemia-lymphoma cells by reducing DNA double-strand repair

  • Authors:
    • Liang Li
    • Shiguang Ye
    • Meng Yang
    • Wenlei Yu
    • Zhuoyi Fan
    • Hong Zhang
    • Jiong Hu
    • Aibin Liang
    • Wenjun Zhang
  • View Affiliations

  • Published online on: September 18, 2015     https://doi.org/10.3892/or.2015.4287
  • Pages: 2935-2942
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Abstract

Most chemotherapy drugs used for the treatment of adult T-cell leukemia-lymphoma (ATL) cause cell death directly by inducing DNA damage, which can be repaired via several DNA repair pathways. Enhanced activity of DNA damage repair systems contributes to ATL resistance to chemotherapies. Targeting DNA repair pathways is a promising strategy for the sensitization of ATL cells to chemotherapeutic drugs. in the present study, inhibition of SIRT1 deacetylase by shRNA sensitized Jurkat cells to etoposide by reducing the activity of non-homologous end joining (NHEJ) and homologous recombination (HR). Silencing of SIRT1 deacetylase by shRNA resulted in enhanced apoptosis and cell cycle arrest, while reduced colony formation of Jurkat cells after etoposide treatment was accompanied by elevated acetylation of FOXO1. Furthermore, inhibition of SIRT1 led to decreased activity of DNA damage repair by NHEJ and HR, accompanied by increased Ku70 acetylation. Furthermore, SIRT1 downregulation prolonged the survival time of Jurkat-xenografted mice. These results suggested that SIRT1 promotes DNA double‑strand repair pathways in Jurkat cells by deacetylating Ku70, and increases cell proliferation by deacetylating FOXO1. The results suggest that SIRT1 is a potential target for the development of combinatorial treatment for ATL.
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December-2015
Volume 34 Issue 6

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

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Spandidos Publications style
Li L, Ye S, Yang M, Yu W, Fan Z, Zhang H, Hu J, Liang A and Zhang W: SIRT1 downregulation enhances chemosensitivity and survival of adult T-cell leukemia-lymphoma cells by reducing DNA double-strand repair. Oncol Rep 34: 2935-2942, 2015.
APA
Li, L., Ye, S., Yang, M., Yu, W., Fan, Z., Zhang, H. ... Zhang, W. (2015). SIRT1 downregulation enhances chemosensitivity and survival of adult T-cell leukemia-lymphoma cells by reducing DNA double-strand repair. Oncology Reports, 34, 2935-2942. https://doi.org/10.3892/or.2015.4287
MLA
Li, L., Ye, S., Yang, M., Yu, W., Fan, Z., Zhang, H., Hu, J., Liang, A., Zhang, W."SIRT1 downregulation enhances chemosensitivity and survival of adult T-cell leukemia-lymphoma cells by reducing DNA double-strand repair". Oncology Reports 34.6 (2015): 2935-2942.
Chicago
Li, L., Ye, S., Yang, M., Yu, W., Fan, Z., Zhang, H., Hu, J., Liang, A., Zhang, W."SIRT1 downregulation enhances chemosensitivity and survival of adult T-cell leukemia-lymphoma cells by reducing DNA double-strand repair". Oncology Reports 34, no. 6 (2015): 2935-2942. https://doi.org/10.3892/or.2015.4287