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

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.

Keywords: Zinc finger antisense 1; cell viability; cisplatin sensitivity; glioma; long non-coding RNAs.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Female
  • Gene Knockdown Techniques
  • Glioma / drug therapy*
  • Glioma / genetics*
  • Glioma / metabolism
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism

Substances

  • Antineoplastic Agents
  • MIRN432 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • ZFAS1 long non-coding RNA, human
  • Cisplatin