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

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Long non-coding RNA OIP5-AS1 inhibition upregulates microRNA-129-5p to repress resistance to temozolomide in glioblastoma cells via downregulating IGF2BP2
Cell Biology and Toxicology ( IF 6.1 ) Pub Date : 2021-06-16 , DOI: 10.1007/s10565-021-09614-z
Xuan Wang ₁ , Xudong Li ₁ , Yan Zhou ₁ , Xing Huang ₁ , Xiaobing Jiang ₁

Affiliation

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.

Graphical Abstract

中文翻译：

长链非编码 RNA OIP5-AS1 抑制上调 microRNA-129-5p，通过下调 IGF2BP2 抑制胶质母细胞瘤细胞对替莫唑胺的耐药性

客观的

长链非编码RNA（lncRNA）和miRNA（miRNA）参与肿瘤，而lncRNA OIP5反义RNA 1（OIP5-AS1）和miR-129-5p对胶质母细胞瘤（GBM）的影响还有待进一步研究。我们旨在探索 OIP5-AS1/miR-129-5p/胰岛素样生长因子 2 mRNA 结合蛋白 2 (IGF2BP2) 轴在 GBM 进展中的作用。

方法

确定组织中的 OIP5-AS1、miR-129-5p 和 IGF2BP2 表达。建立了替莫唑胺 (TMZ) 抗性 GBM 细胞，并用相关质粒转染以改变 OIP5-AS1、IGF2BP2 或 miR-129-5p 表达。然后，评估生存力、增殖、细胞凋亡和体内肿瘤生长。确定了 OIP5-AS1 的亚细胞定位，并证实了 OIP5-AS1 与 miR-129-5p 之间以及 miR-129-5p 与 IGF2BP2 之间的结合关系。

结果

OIP5-AS1 和 IGF2BP2 在 GBM 中被上调，而 miR-129-5p 被下调。OIP5-AS1 沉默或 miR-129-5p 过表达抑制 GBM 细胞对 TMZ 的化学耐药性和增殖，并促进细胞凋亡。MiR-129-5p 下调或 IGF2BP2 上调逆转了 OIP5-AS1 沉默对 GBM 细胞的作用。OIP5-AS1 海绵化 miR-129-5p 和 miR-129-5p 靶向 IGF2BP2。