Knockdown of Bmi1 inhibits the stemness properties and tumorigenicity of human bladder cancer stem cell-like side population cells.
Knockdown of Bmi1 inhibits the stemness properties and tumorigenicity of human bladder cancer stem cell-like side population cells.
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DOI：
10.3892/or.2013.2919
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发表时间：
2014-02
期刊：
影响因子：
4.2
通讯作者：
Dingjun Zhu;X. Wan;Hai Huang;Xu Chen;Wu Liang;Fengjin Zhao;Tianxin Lin;Jinli Han;W. Xie
中科院分区：
文献类型：
--
作者：
Dingjun Zhu;X. Wan;Hai Huang;Xu Chen;Wu Liang;Fengjin Zhao;Tianxin Lin;Jinli Han;W. Xie
B细胞特异性莫洛尼鼠白血病病毒插入位点1（Bmi 1）直接参与癌症干细胞（CSC）的细胞生长、增殖和自我更新。本研究的目的是评估Bmi 1在维持人膀胱CSC样侧群（SP）细胞的干细胞特性和致瘤性中的作用。使用Hoechst 33342染色通过流式细胞术分选SP细胞。采用定量PCR、免疫荧光和Western blotting分析SP和非SP（NSP）细胞中Bmi 1 mRNA和蛋白的表达。检测SP细胞的增殖、迁移、自我更新、耐化疗和细胞周期进程等干细胞特性。还在Bmi 1沉默后的人膀胱癌异种移植物中评估肿瘤形成。SP细胞中Bmi 1 mRNA的表达较NSP细胞中Bmi 1 mRNA的表达上调。在SP细胞中敲低Bmi 1导致细胞增殖、迁移和肿瘤球形成的抑制，对顺铂的敏感性增强，并且细胞周期停滞在G 0/G1期。Bmi 1基因敲低通过p16 INK 4a/p14 ARF位点的去抑制来抑制细胞周期进程。Bmi 1-siRNA SP细胞不能在受体小鼠中产生肿瘤，而皮下注射scramble-siRNA SP细胞形成典型的尿路上皮癌。Bmi 1对维持人膀胱CSC样细胞的干细胞特性和致瘤性至关重要。Bmi 1可能是一个潜在的治疗靶点，用于根除膀胱癌中的CSC。
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.