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

Xu,Xin-Hua; Liu,Xiao-Yan; Su,Jin; Li,Dao-Jun; Huang,Qiao; Lu,Ming‑Qian; Yi,Fang; Ren,Jing-Hua; Chen,Wei-Hong

doi:10.3892/or.2014.3267

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
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Affiliations: Department of Oncology, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang, Hubei, P.R. China, Oncology Institute, China Three Gorges University, Yichang, Hubei, P.R. China, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China
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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