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微小RNA-24-3p通过靶向死亡结构域蛋白(DEDD)调控膀胱癌细胞的增殖、迁移、侵袭和自噬。

miR-24-3p regulates bladder cancer cell proliferation, migration, invasion and autophagy by targeting DEDD.

作者信息

Yu Guoqiang, Jia Zhaohui, Dou Zhongling

机构信息

Department of Urological Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.

出版信息

Oncol Rep. 2017 Feb;37(2):1123-1131. doi: 10.3892/or.2016.5326. Epub 2016 Dec 16.

Abstract

microRNAs (miRNAs), a class of small non-coding RNA molecules, can regulate gene expression by interacting with the 3'-untranslated regions (3'UTR) of target genes and influence various biological processes. We investigated the potential role of miR-24-3p in the development of bladder cancer by regulating DEDD, a member of the death effector domain-containing protein family. First, we found that miR-24-3p was highly expressed and that DEDD was expressed at a low level in bladder cancer tissues compared with that in adjacent bladder tissues by qRT-PCR (P<0.0001). Second, we found that miR-24-3p promoted the proliferation ability of bladder cancer cells using the MTT assay and colony forming assay; and showed that miR-24-3p accelerated the migration and invasion of bladder cancer cells using migration and invasion assays (P<0.05). Moreover, miR-24-3p inhibited apoptosis of bladder cancer cells, as shown by flow cytometry (P<0.05). Western blot results demonstrated that miR-24-3p participated in autophagy of bladder cancer cells by DEDD. In addition, the tumor formation assay showed that miR-24-3p promoted the growth of bladder tumor in vivo. Furthermore, the luciferase reporter gene assay indicated that miR-24-3p suppressed DEDD gene transcription. Therefore, our study indicated that miR-24-3p promoted bladder cancer progression by inhibiting DEDD.

摘要

微小RNA(miRNA)是一类小的非编码RNA分子,可通过与靶基因的3'非翻译区(3'UTR)相互作用来调节基因表达,并影响各种生物学过程。我们通过调控含死亡效应结构域蛋白家族成员DEDD,研究了miR-24-3p在膀胱癌发生发展中的潜在作用。首先,我们通过qRT-PCR发现,与相邻膀胱组织相比,miR-24-3p在膀胱癌组织中高表达,而DEDD表达水平较低(P<0.0001)。其次,我们使用MTT法和集落形成试验发现miR-24-3p促进了膀胱癌细胞的增殖能力;并通过迁移和侵袭试验表明miR-24-3p加速了膀胱癌细胞的迁移和侵袭(P<0.05)。此外,流式细胞术结果显示miR-24-3p抑制了膀胱癌细胞的凋亡(P<0.05)。蛋白质免疫印迹结果表明,miR-24-3p通过DEDD参与了膀胱癌细胞的自噬过程。另外,肿瘤形成试验表明miR-24-3p在体内促进了膀胱肿瘤的生长。此外,荧光素酶报告基因试验表明miR-24-3p抑制了DEDD基因的转录。因此,我们的研究表明miR-24-3p通过抑制DEDD促进了膀胱癌的进展。

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