miR-148-3p 和 miR-152-3p 通过抑制 KLF4 协同调控前列腺癌的进展。

miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4.

机构信息

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

School of Medicine, Shandong University, Jinan, China.

出版信息

J Cell Biochem. 2019 Oct;120(10):17228-17239. doi: 10.1002/jcb.28984. Epub 2019 May 19.

DOI:10.1002/jcb.28984

PMID:31104329

Abstract

BACKGROUND

miR-148-3p and miR-152-3p as the tumor suppressors have been reported in various cancer types. Our study is aimed to discuss the synergistic effect of miR-148-3p and miR-152-3p in prostate cancer (PCa).

METHODS

Bioinformatics algorithm and luciferase reporter assays were used to verify whether miR-148-3p and 152-3p could bind with the 3'-untranslated region (3'-UTR) of Kruppel-like factor 4 (KLF4). PCa cell growth in vivo was analyzed using the mouse xenograft tumor model.

RESULTS

miR-148-3p and miR-152-3p were reduced in PCa tumor tissues. Moreover, the protein expression of KLF4 was increased in PCa tissues. The 3'-UTR of KLF4 contained the conserved binding sites with miR-148-3p and miR-152-3p. The mimics or inhibitors of miR-148-3p and/or miR-152-3p could downregulated or upregulated KLF4 expression, respectively. miR-148-3p and miR-152-3p-induced PCa cell growth inhibition were observed both in vivo and in vitro. KLF4 overexpression had the ability to neutralize the antitumor effect of miR-148-3p/152-3p in vivo and in vitro.

CONCLUSION

miR-148-3p/152-3p family could serve as tumor suppressors in PCa via repressing KLF4.

摘要

背景

miR-148-3p 和 miR-152-3p 作为肿瘤抑制因子在多种癌症类型中已有报道。我们的研究旨在探讨 miR-148-3p 和 miR-152-3p 在前列腺癌（PCa）中的协同作用。

方法

使用生物信息学算法和荧光素酶报告基因实验来验证 miR-148-3p 和 152-3p 是否可以与 Kruppel 样因子 4（KLF4）的 3'-非翻译区（3'-UTR）结合。使用小鼠异种移植肿瘤模型分析 PCa 细胞的体内生长情况。

结果

miR-148-3p 和 miR-152-3p 在 PCa 肿瘤组织中表达降低。此外，PCa 组织中 KLF4 蛋白表达增加。KLF4 的 3'-UTR 含有与 miR-148-3p 和 miR-152-3p 保守结合的位点。miR-148-3p 和 miR-152-3p 的模拟物或抑制剂分别可以下调或上调 KLF4 的表达。miR-148-3p 和 miR-152-3p 诱导的 PCa 细胞生长抑制在体内和体外均有观察到。KLF4 过表达能够在体内和体外中和 miR-148-3p/152-3p 的抗肿瘤作用。