title: 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.affiliation: Department of Oncology, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang, Hubei, P.R. China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Xu
authors.affiliation: Department of Oncology, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang, Hubei, P.R. China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Oncology Institute, China Three Gorges University, Yichang, Hubei, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Su
authors.affiliation: Oncology Institute, China Three Gorges University, Yichang, Hubei, P.R. China.
authors.forename: Dao-Jun
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Oncology Institute, China Three Gorges University, Yichang, Hubei, P.R. China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Oncology, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang, Hubei, P.R. China.
authors.forename: Ming-Qian
authors.initials: MQ
authors.lastname: Lu
authors.affiliation: Oncology Institute, China Three Gorges University, Yichang, Hubei, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yi
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Ren
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000532:radiotherapy*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000528:radiation effects; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: C069077:BMI1 protein, human; C497483:CD44 protein, human; C468783:H2AX protein, human; D006657:Histones; D018960:Hyaluronan Receptors; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1