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ZFAS1 敲低通过上调胶质瘤细胞中的 miR-432-5p 抑制活力并增强顺铂细胞毒性。

ZFAS1 knockdown inhibits viability and enhances cisplatin cytotoxicity by up-regulating miR-432-5p in glioma cells.

机构信息

Department of Neurosurgery, Shanxian Central Hospital, Heze, China.

出版信息

Basic Clin Pharmacol Toxicol. 2019 Dec;125(6):518-526. doi: 10.1111/bcpt.13286. Epub 2019 Jul 19.

Abstract

BACKGROUND

Long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) is a novel vital oncogenic lncRNA that is dysregulated in various types of cancers, including glioma. According to TargetScan prediction, miR-432-5p is a target of ZFAS1. Herein, we aimed to determine whether there was a correlation between ZFAS1 and miR-432-5p and to explore their roles in glioma.

METHODS

The expression levels of ZFAS1 and microRNA (miR)-432-5p in clinical tissues and cell lines were measured using RT-qPCR. Cell viability was detected using MTT assay. Cell apoptosis was examined using flow cytometry. The association between ZFAS1 and miR-432-5p was confirmed using luciferase reporter and RNA pull-down assays.

RESULTS

Zinc finger antisense 1 expression was up-regulated, while miR-432-5p expression was down-regulated in both glioma tissues and cells. Knockdown of ZFAS1 and miR-432-5p overexpression inhibited cell viability and enhanced the chemosensitivity of glioma cells to cisplatin. MiR-432-5p was a direct target of ZFAS1 in glioma cells. Inhibition of miR-432-5p blocked the effects of ZFAS1 knockdown on cell viability and cisplatin sensitivity.

CONCLUSIONS

Knockdown of ZFAS1 inhibited the viability and enhanced cisplatin sensitivity via targeting miR-432-5p in glioma cells.

摘要

背景

长链非编码 RNA(lncRNA)锌指反义 1(ZFAS1)是一种新型重要致癌 lncRNA,在包括神经胶质瘤在内的多种类型的癌症中失调。根据 TargetScan 预测,miR-432-5p 是 ZFAS1 的一个靶标。在此,我们旨在确定 ZFAS1 和 miR-432-5p 之间是否存在相关性,并探讨它们在神经胶质瘤中的作用。

方法

使用 RT-qPCR 测量临床组织和细胞系中 ZFAS1 和 microRNA(miR)-432-5p 的表达水平。使用 MTT 测定法检测细胞活力。通过流式细胞术检查细胞凋亡。使用荧光素酶报告和 RNA 下拉测定法证实 ZFAS1 和 miR-432-5p 之间的关联。

结果

ZFAS1 表达上调,而 miR-432-5p 在神经胶质瘤组织和细胞中均下调。ZFAS1 敲低和 miR-432-5p 过表达抑制了神经胶质瘤细胞的活力并增强了它们对顺铂的化疗敏感性。miR-432-5p 是神经胶质瘤细胞中 ZFAS1 的直接靶标。抑制 miR-432-5p 阻断了 ZFAS1 敲低对细胞活力和顺铂敏感性的影响。

结论

在神经胶质瘤细胞中,ZFAS1 敲低通过靶向 miR-432-5p 抑制细胞活力并增强顺铂敏感性。

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