Long non-coding RNA OIP5-AS1 inhibition upregulates microRNA-129-5p to repress resistance to temozolomide in glioblastoma cells via downregulating IGF2BP2

Cell Biol Toxicol. 2022 Dec;38(6):963-977. doi: 10.1007/s10565-021-09614-z. Epub 2021 Jun 16.

Abstract

Objective: Long non-coding RNAs (lncRNAs) and miRNAs (miRNAs) participate in tumors, while the effects of lncRNA OIP5 antisense RNA 1 (OIP5-AS1) and miR-129-5p on glioblastoma (GBM) remain to be further studied. We aim to explore the role of OIP5-AS1/miR-129-5p/insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) axis in GBM progression.

Methods: OIP5-AS1, miR-129-5p and IGF2BP2 expression in tissues was determined. Temozolomide (TMZ)-resistant GBM cells were established and transfected with relative plasmid to alter OIP5-AS1, IGF2BP2 or miR-129-5p expression. Then, the viability, proliferation, apoptosis and in vivo tumor growth were assessed. The subcellular localization of OIP5-AS1 was determined, and the binding relationships between OIP5-AS1 and miR-129-5p, and between miR-129-5p and IGF2BP2 were confirmed.

Results: OIP5-AS1 and IGF2BP2 were upregulated whereas miR-129-5p was downregulated in GBM. OIP5-AS1 silencing or miR-129-5p overexpression inhibited GBM cell chemoresistance to TMZ and proliferation, and promoted cell apoptosis. MiR-129-5p downregulation or IGF2BP2 upregulation reversed the role of OIP5-AS1 silencing on GBM cells. OIP5-AS1 sponged miR-129-5p and miR-129-5p targeted IGF2BP2.

Conclusion: OIP5-AS1 inhibition upregulated miR-129-5p to repress resistance to TMZ in GBM cells via downregulating IGF2BP2.

Keywords: Drug resistance; Glioblastoma; Insulin-like growth factor 2 mRNA-binding protein 2; Long non-coding RNA OIP5 antisense RNA 1; MicroRNA-129-5p; Temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioblastoma* / drug therapy
  • Glioblastoma* / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Temozolomide / pharmacology

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • Temozolomide
  • IGF2BP2 protein, human
  • RNA-Binding Proteins
  • Mirn129 microRNA, human