shRNA targeting Bmi-1 sensitizes CD44+ nasopharyngeal cancer stem-like cells to radiotherapy

  • Authors:
    • Xin-Hua Xu
    • Xiao-Yan Liu
    • Jin Su
    • Dao-Jun  Li
    • Qiao  Huang
    • Ming‑Qian  Lu
    • Fang  Yi
    • Jing-Hua  Ren
    • Wei-Hong Chen
  • View Affiliations

  • Published online on: June 13, 2014     https://doi.org/10.3892/or.2014.3267
  • Pages: 764-770
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Abstract

Accumulating evidence indicates that cancer stem cells (CSCs) are involved in resistance to radiation therapy (RT). Bmi-1, a member of the Polycomb family of transcriptional repressors, is essential for maintaining the self-renewal abilities of stem cells and overexpression of Bmi-1 correlates with cancer therapy failure. Our previous study identified that the CD44+ nasopharyngeal cancer (NPC) cells may be assumed as one of markers of nasopharyngeal carcinoma cancer stem cell-like cells (CSC-LCs) and Bmi-1 is overexpressed in CD44+ NPC. In the present study, we used RNA interference technology to knock down the expression of Bmi-1 in CD44+ NPC cells, and then measured the radiation response by clonogenic cell survival assay. DNA repair was monitored by γH2AX foci formation. Bmi-1 downstream relative gene and protein expression of p16, p14, p53 were assessed by western blotting and real-time PCR. Cell cycle and apoptosis were detected by flow cytometry assays. We found that Bmi-1 knockdown prolonged G1 and enhanced the radiation-induced G2/M arrest, inhibited DNA damage repair, elevated protein p16, p14 and p53 expression, leading to increased apoptosis in the radiated CD44+ cells. These data suggest that Bmi-1 downregulation increases the radiosensitivity to CD44+ NPC CSC-LCs. Bmi-1 is a potential target for increasing the sensitivity of NPC CSCs to radiotherapy.
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August-2014
Volume 32 Issue 2

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

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Spandidos Publications style
Xu X, Liu X, Su J, Li D, Huang Q, Lu MQ, Yi F, Ren J and Chen W: shRNA targeting Bmi-1 sensitizes CD44+ nasopharyngeal cancer stem-like cells to radiotherapy. Oncol Rep 32: 764-770, 2014.
APA
Xu, X., Liu, X., Su, J., Li, D., Huang, Q., Lu, M. ... Chen, W. (2014). shRNA targeting Bmi-1 sensitizes CD44+ nasopharyngeal cancer stem-like cells to radiotherapy. Oncology Reports, 32, 764-770. https://doi.org/10.3892/or.2014.3267
MLA
Xu, X., Liu, X., Su, J., Li, D., Huang, Q., Lu, M., Yi, F., Ren, J., Chen, W."shRNA targeting Bmi-1 sensitizes CD44+ nasopharyngeal cancer stem-like cells to radiotherapy". Oncology Reports 32.2 (2014): 764-770.
Chicago
Xu, X., Liu, X., Su, J., Li, D., Huang, Q., Lu, M., Yi, F., Ren, J., Chen, W."shRNA targeting Bmi-1 sensitizes CD44+ nasopharyngeal cancer stem-like cells to radiotherapy". Oncology Reports 32, no. 2 (2014): 764-770. https://doi.org/10.3892/or.2014.3267