通过慢病毒介导的RNA干扰靶向PPM1D可抑制膀胱癌细胞的致瘤性。
Targeting PPM1D by lentivirus-mediated RNA interference inhibits the tumorigenicity of bladder cancer cells.
作者信息
Wang W, Zhu H, Zhang H, Zhang L, Ding Q, Jiang H
机构信息
Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Department of the Intensive Care Unit, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
Braz J Med Biol Res. 2014 Dec;47(12):1044-9. doi: 10.1590/1414-431x20143645. Epub 2014 Sep 23.
Protein phosphatase magnesium/manganese-dependent 1D (PPM1D) is a p53-induced phosphatase that functions as a negative regulator of stress response pathways and has oncogenic properties. However, the functional role of PPM1D in bladder cancer (BC) remains largely unknown. In the present study, lentivirus vectors carrying small hairpin RNA (shRNA) targeting PPM1D were used to explore the effects of PPM1D knockdown on BC cell proliferation and tumorigenesis. shRNA-mediated knockdown of PPM1D significantly inhibited cell growth and colony forming ability in the BC cell lines 5637 and T24. Flow cytometric analysis showed that PPM1D silencing increased the proportion of cells in the G0/G1 phase. Downregulation of PPM1D also inhibited 5637 cell tumorigenicity in nude mice. The results of the present study suggest that PPM1D plays a potentially important role in BC tumorigenicity, and lentivirus-mediated delivery of shRNA against PPM1D might be a promising therapeutic strategy for the treatment of BC.
蛋白磷酸酶镁/锰依赖1D（PPM1D）是一种p53诱导的磷酸酶，作为应激反应途径的负调节因子发挥作用，并具有致癌特性。然而，PPM1D在膀胱癌（BC）中的功能作用仍 largely未知。在本研究中，携带靶向PPM1D的小发夹RNA（shRNA）的慢病毒载体被用于探索PPM1D敲低对BC细胞增殖和肿瘤发生的影响。shRNA介导的PPM1D敲低显著抑制了BC细胞系5637和T24中的细胞生长和集落形成能力。流式细胞术分析表明，PPM1D沉默增加了G0/G1期细胞的比例。PPM1D的下调也抑制了5637细胞在裸鼠中的致瘤性。本研究结果表明，PPM1D在BC肿瘤发生中发挥潜在重要作用，慢病毒介导的针对PPM1D的shRNA递送可能是治疗BC的一种有前景的治疗策略。
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