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环状 RNA NR3C1 通过海绵吸附 miR-27a-3p 和下调细胞周期蛋白 D1 的表达来抑制膀胱癌细胞的增殖。

CircNR3C1 inhibits proliferation of bladder cancer cells by sponging miR-27a-3p and downregulating cyclin D1 expression.

机构信息

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Urology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

Cancer Lett. 2019 Sep 28;460:139-151. doi: 10.1016/j.canlet.2019.06.018. Epub 2019 Jun 27.

DOI:10.1016/j.canlet.2019.06.018
PMID:31255724
Abstract

Accumulating evidences suggest that circular RNAs play vital roles in human cancers. Previously, we found that circHIPK3 suppressed invasion of bladder cancer cells via sponging miR-558 and downregulating heparanase expression. In this study, we discovered that a circular RNA derived from NR3C1 (circNR3C1) was downregulated in bladder cancer tissues and cell lines according to RNA-Seq data and qRT-PCR analysis. Functionally, we found that overexpression of circNR3C1 could significantly inhibit cell cycle progression and proliferation of bladder cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistically, we demonstrated that circNR3C1 possessed four targeting sites of miR-27a-3p and could effectively sponge miR-27a-3p to suppress the expression of cyclin D1. Furthermore, we revealed that miR-27a-3p functioned as an oncogene through interacting with 5'UTR of cyclin D1 to enhance its expression, which led to promote cell cycle progression and proliferation in bladder cancer cells. Conclusively, our findings further confirm the hypothesis that circRNAs function as "microRNA sponges", and our data suggest that circNR3C1 and miR-27a-3p would be potential therapeutic targets for bladder cancer treatment.

摘要

越来越多的证据表明,环状 RNA 在人类癌症中发挥着重要作用。此前,我们发现 circHIPK3 通过海绵吸附 miR-558 和下调乙酰肝素酶表达来抑制膀胱癌细胞的侵袭。在这项研究中,我们发现根据 RNA-Seq 数据和 qRT-PCR 分析,NR3C1 来源的环状 RNA (circNR3C1) 在膀胱癌组织和细胞系中表达下调。功能上,我们发现过表达 circNR3C1 可显著抑制膀胱癌细胞在体外的细胞周期进程和增殖,并抑制体内肿瘤生长。从机制上讲,我们证明 circNR3C1 具有 miR-27a-3p 的四个靶向位点,并能有效吸附 miR-27a-3p 抑制细胞周期蛋白 D1 的表达。此外,我们揭示了 miR-27a-3p 通过与 cyclin D1 的 5'UTR 相互作用来增强其表达,从而促进膀胱癌细胞的细胞周期进程和增殖,从而发挥致癌基因的作用。总之,我们的研究结果进一步证实了环状 RNA 作为“miRNA 海绵”发挥作用的假设,并且我们的数据表明 circNR3C1 和 miR-27a-3p 可能是膀胱癌治疗的潜在治疗靶点。

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