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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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 |
Journal | Oncology reports
(Oncol Rep)
Vol. 32
Issue 2
Pg. 764-70
(Aug 2014)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 24927072
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BMI1 protein, human
- CD44 protein, human
- H2AX protein, human
- Histones
- Hyaluronan Receptors
- RNA, Small Interfering
- Polycomb Repressive Complex 1
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Topics |
- Apoptosis
(radiation effects)
- Cell Line, Tumor
- Gene Expression Regulation, Neoplastic
(radiation effects)
- Gene Knockdown Techniques
- Histones
(metabolism)
- Humans
- Hyaluronan Receptors
(metabolism)
- Nasopharyngeal Neoplasms
(radiotherapy)
- Neoplastic Stem Cells
(metabolism, radiation effects)
- Polycomb Repressive Complex 1
(genetics, metabolism)
- RNA, Small Interfering
(genetics, metabolism)
- Signal Transduction
(radiation effects)
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