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

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.

• 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)

Chemical References

• BMI1 protein, human
• CD44 protein, human
• H2AX protein, human
• Histones
• Hyaluronan Receptors
• RNA, Small Interfering
• Polycomb Repressive Complex 1

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)