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Am J Transl Res：或可通过靶向miR-204/ZEB1治疗晚期/耐药前列腺癌患者

2017-09-04 MedSci MedSci原创

miR-204/ZEB1前列腺癌
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microRNAs (miRNAs)所致的表观基因失活在肿瘤恶性转化、防止凋亡、耐药性和转移中起着至关重要的作用。研究已经发现前列腺癌（PC）中miR-204的表达失调，且认为miR-204与肿瘤耐药性的发生相关。然而，miR-204在PC中发挥作用的详细机制，特别是耐药性，尚未完全阐明。本研究中，研究人员利用miRNA微阵列分析发现，与药物敏感的PC组织及良性前列腺增生组织中相比，耐药PC组织中

microRNAs (miRNAs)所致的表观基因失活在肿瘤恶性转化、防止凋亡、耐药性和转移中起着至关重要的作用。研究已经发现前列腺癌（PC）中miR-204的表达失调，且认为miR-204与肿瘤耐药性的发生相关。然而，miR-204在PC中发挥作用的详细机制，特别是耐药性，尚未完全阐明。

本研究中，研究人员利用miRNA微阵列分析发现，与药物敏感的PC组织及良性前列腺增生组织中相比，耐药PC组织中miR-204的表达下调。qPCR验证了基因芯片的检测结果。体外实验研究同样发现了PC表达水平的变化。

过表达miR-204可明显减弱PC-3-R细胞对多西他赛的耐药性，并可促进细胞凋亡，而敲除miR-204则可有效降低多西紫杉醇诱导的细胞死亡并抑制细胞凋亡。具体来说，miR-204 可直接靶向锌指结构转录因子1 (ZEB1) 的3’非翻译区并可通过抑制翻译来抑制其蛋白的表达。此外，抑制ZEB1能有效改善miR-204不足引发的PC细胞的耐药性。

总之，该研究结果表明，耐药性的PC组织及细胞中miR-204的表达下调，miR-204/ZEB1或可作为晚期/耐药PC患者的辅助治疗靶点。

原始出处：

Guanlin Wu, Jian Wang, et al., microRNA-204 modulates chemosensitivity and apoptosis of prostate cancer cells by targeting zinc-finger E-box-binding homeobox 1 (ZEB1). Am J Transl Res. 2017; 9(8): 3599–3610. Published online 2017 Aug 15.

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    2018-06-16 bsmagic9140

    #TRA#

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    2018-03-22 smallant2002

    #miR#

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    2017-09-09 ms3025846204744509

    #Transl#

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    2017-09-04 189****7206

    学习了受益匪浅

    0