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微小RNA对p21(WAF1/CIP1)的上调作用及其在膀胱癌细胞中的意义

Up-regulation of p21(WAF1/CIP1) by miRNAs and its implications in bladder cancer cells.

作者信息

Wang Chenghe, Chen Zhong, Ge Qiangqiang, Hu Junhui, Li Fan, Hu Jia, Xu Hua, Ye Zhangqun, Li Long-Cheng

机构信息

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan 430030, Hubei, China.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan 430030, Hubei, China.

出版信息

FEBS Lett. 2014 Dec 20;588(24):4654-64. doi: 10.1016/j.febslet.2014.10.037. Epub 2014 Nov 11.

Abstract

We have previously reported that synthetic dsRNA can activate p21 expression by targeting the p21 promoter, thereby suppressing the proliferation of human bladder cancer cells. As complementarity between dsRNA and its target sequences is necessary for RNA activation, miRNAs may also trigger p21 expression through the same mechanism. Here, the expression levels of three miRNAs (miR-370, miR-1180 and miR-1236) decreased in bladder cancer tissues compared to healthy controls and the levels of these mRNAs positively correlated with p21 mRNA levels. The three miRNAs induced nuclear p21 expression through p21-promoter binding. Overexpression of the three miRNAs inhibited the proliferation of bladder cancer cells mainly by regulating p21. Therefore, these miRNAs could be candidates for anti-cancer drugs.

摘要

我们之前曾报道,合成双链RNA(dsRNA)可通过靶向p21启动子激活p21表达,从而抑制人膀胱癌细胞的增殖。由于双链RNA与其靶序列之间的互补性是RNA激活所必需的,因此微小RNA(miRNA)也可能通过相同机制触发p21表达。在此,与健康对照相比,三种miRNA(miR-370、miR-1180和miR-1236)在膀胱癌组织中的表达水平降低,且这些miRNA的水平与p21 mRNA水平呈正相关。这三种miRNA通过与p21启动子结合诱导细胞核p21表达。这三种miRNA的过表达主要通过调节p21抑制膀胱癌细胞的增殖。因此,这些miRNA可能成为抗癌药物的候选物。

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