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TP53INP1 3'-非编码区通过调节miRNA活性,作为竞争性内源RNA发挥抑制胶质瘤细胞转移的作用。

TP53INP1 3'-UTR functions as a ceRNA in repressing the metastasis of glioma cells by regulating miRNA activity.

作者信息

Wang Yi, Lin Guihua

机构信息

Department of Neurosurgery, The Cangzhou Central Hospital, Cangzhou, 061001, China.

Department of Blood Transfusion, The Affiliated Ningde Municipal Hospital, Fujian Medical University, Ningde, 352000, China.

出版信息

Biotechnol Lett. 2016 Oct;38(10):1699-707. doi: 10.1007/s10529-016-2159-3. Epub 2016 Jun 24.

Abstract

OBJECTIVES

To explore the effects of the competitive endogenous RNA (ceRNA) network between TP53INP1 and E-cadherin on the invasion and migration of glioma.

RESULTS

TP53INP1 and E-cadherin mRNA and protein were significantly overexpressed in normal brain tissues compared with glioma tissue specimens and correlated with the grades of glioma negatively. The expression of TP53INP1 and E-cadherin were correlated positively. Patients with higher TP53INP1 or E-cadherin expression had longer overall survival. Moreover, TP53INP1 3'-UTR inhibited glioma cell proliferation, invasion and proliferation; Furthermore, the 3'-UTRs of TP53INP1 and E-cadherin harboured seven identical miRNAs binding sites, and TP53INP1 3'-UTR could increase the expression of E-cadherin and decrease the expression of vimentin thus repressing the epithelial-mesenchymal transition (EMT). However, the coding sequence of TP53INP1 could not increase the expression of E-cadherin and the inhibitory effect on EMT of TP53INP1 3'-UTR was reversed by the siRNA against Dicer.

CONCLUSIONS

TP53INP1 3'-UTR could inhibit the EMT, thus hindering the migration and invasion of glioma via acting as a ceRNA for E-cadherin.

摘要

目的

探讨TP53INP1与E-钙黏蛋白之间的竞争性内源性RNA(ceRNA)网络对胶质瘤侵袭和迁移的影响。

结果

与胶质瘤组织标本相比,TP53INP1和E-钙黏蛋白的mRNA及蛋白在正常脑组织中显著过表达,且与胶质瘤分级呈负相关。TP53INP1与E-钙黏蛋白的表达呈正相关。TP53INP1或E-钙黏蛋白表达较高的患者总生存期较长。此外,TP53INP1的3'-UTR抑制胶质瘤细胞增殖、侵袭和迁移;而且,TP53INP1和E-钙黏蛋白的3'-UTR含有7个相同的微小RNA(miRNA)结合位点,TP53INP1的3'-UTR可增加E-钙黏蛋白的表达并降低波形蛋白的表达,从而抑制上皮-间质转化(EMT)。然而,TP53INP1的编码序列不能增加E-钙黏蛋白的表达,且针对Dicer的小干扰RNA(siRNA)可逆转TP53INP1的3'-UTR对EMT的抑制作用。

结论

TP53INP1的3'-UTR可抑制EMT,从而通过作为E-钙黏蛋白的ceRNA来阻碍胶质瘤的迁移和侵袭。

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