长链非编码 RNA ZEB2-AS1 通过调节 miR-27b 促进膀胱癌细胞增殖并抑制细胞凋亡。

LncRNA ZEB2-AS1 promotes bladder cancer cell proliferation and inhibits apoptosis by regulating miR-27b.

机构信息

Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China.

出版信息

Biomed Pharmacother. 2017 Dec;96:299-304. doi: 10.1016/j.biopha.2017.08.060. Epub 2017 Nov 24.

DOI:10.1016/j.biopha.2017.08.060

PMID:28992472

Abstract

BACKGROUND

The aim of this study was to explore the role of lncRNA zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1), as a new tumor-associated lncRNA, in bladder cancer (BC) pathogenesis.

METHODS

BC tissues and tumor-adjacent normal bladder tissues were collected for detection of the expression profile of ZEB2-AS1 and miR-27b in BC. The endogenous expression of ZEB2-AS1 and miR-27b was modulated by the recombinant expression vector in vitro. The interaction between ZEB2-AS1 and miR-27b was identified by luciferase report gene assays and RNA immunoprecipitation (RIP) assays. The proliferation and apoptosis of BC cells was determined using CCK-8 assays and flow cytometric analysis.

RESULTS

The expression of ZEB2-AS1 was significantly increased in both BC tissues and BC cells (J82, 5637, T24); while miR-27b was down-regulated in BC tissues. More importantly, ZEB2-AS1 was significantly negative correlated with miR-27b expression in BC tissues (R=0.1688, P<0.05). ZEB2-AS1 silencing inhibited BC cell proliferation and promoted apoptosis. Further studies confirmed that miR-27b was negatively regulated by ZEB2-AS1 in BC cells 5637 and T24, and the effects of ZEB2-AS1 on BC cells was mediated by miR-27b.

CONCLUSION

Our data provided strong evidence that ZEB2-AS1 promoted tumorigenesis and development of BC through down-regulating tumor-suppressive miR-27b.

摘要

背景

本研究旨在探讨长链非编码 RNA（lncRNA）锌指 E 盒结合同源盒 2 反义 RNA 1（ZEB2-AS1）作为一种新的肿瘤相关 lncRNA 在膀胱癌（BC）发病机制中的作用。

方法

收集 BC 组织和肿瘤旁正常膀胱组织，检测 BC 中 ZEB2-AS1 和 miR-27b 的表达谱。体外通过重组表达载体调节 ZEB2-AS1 和 miR-27b 的内源性表达。通过荧光素酶报告基因检测和 RNA 免疫沉淀（RIP）实验鉴定 ZEB2-AS1 和 miR-27b 之间的相互作用。通过 CCK-8 检测和流式细胞术分析测定 BC 细胞的增殖和凋亡。

结果

BC 组织和 BC 细胞（J82、5637、T24）中 ZEB2-AS1 的表达均显著升高，而 miR-27b 在 BC 组织中下调。更重要的是，BC 组织中 ZEB2-AS1 与 miR-27b 的表达呈显著负相关（R=0.1688，P<0.05）。ZEB2-AS1 沉默抑制 BC 细胞增殖并促进凋亡。进一步的研究证实，ZEB2-AS1 在 BC 细胞 5637 和 T24 中负调控 miR-27b，ZEB2-AS1 对 BC 细胞的作用是通过 miR-27b 介导的。