title: Knockdown of Bmi1 inhibits the stemness properties and tumorigenicity of human bladder cancer stem cell-like side population cells.
abstract: B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) is directly involved in cell growth, proliferation and self-renewal of cancer stem cells (CSCs). The aim of the present study was to assess the role of Bmi1 in the maintenance of stemness properties and tumorigenicity of human bladder CSC-like side population (SP) cells. SP cells were sorted by flow cytometry using Hoechst 33342 staining. Bmi1 mRNA and protein expression in SP and non-SP (NSP) cells was analyzed by quantitative PCR, immunofluorescence and western blotting. The stemness properties of SP cells included cell proliferation, migration, self-renewal, chemotherapy resistance and cell cycle progression were assessed. Tumor formation was also assessed in human bladder cancer xenografts after Bmi1 silencing. The mRNA expression of Bmi1 was upregulated in SP cells when compared with that in the NSP cells. Knockdown of Bmi1 in SP cells resulted in inhibition of cell proliferation, migration and tumor sphere formation, enhanced sensitivity to cisplatin, and cell cycle arrest in the G0/G1 phase. Bmi1 knockdown inhibited cell cycle progression through derepression of the p16INK4a/p14ARF locus. Bmi1-siRNA SP cells failed to produce tumors in recipient mice, while typical urothelial carcinoma formed from subcutaneously injected scramble-siRNA SP cells. Bmi1 is crucial for the maintenance of stemness properties and tumorigenicity of human bladder CSC-like cells. Bmi1 may be a potential therapeutic target for the eradication of CSCs in bladder cancer.
authors: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
authors: Dingjun
authors: D
authors: Zhu
authors: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, P.R. China.
authors: Xuesi
authors: X
authors: Wan
authors: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
authors: Hai
authors: H
authors: Huang
authors: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
authors: Xu
authors: X
authors: Chen
authors: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
authors: Wu
authors: W
authors: Liang
authors: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
authors: Fengjin
authors: F
authors: Zhao
authors: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
authors: Tianxin
authors: T
authors: Lin
authors: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
authors: Jinli
authors: J
authors: Han
authors: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
authors: Wenlian
authors: W
authors: Xie
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000473:pathology*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D058985:Side-Population Cells / Q000166:cytology / Q000473:pathology*; D018874:Spheroids, Cellular / Q000166:cytology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF / Q000096:biosynthesis / Q000235:genetics; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: C069077:BMI1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025803:Tumor Suppressor Protein p14ARF; D063150:Polycomb Repressive Complex 1