Double-stranded RNA inhibits the growth and migration of malignant gliomas through the activation of the PKR/eIF2α pathway
10.3969/j.issn.1672-8467.2024.03.002
- VernacularTitle:双链RNA通过激活PKR/eIF2α通路抑制恶性胶质瘤生长和迁移
- Author:
Qun YAN
1
;
Sha-Sha BIAN
;
Min-Feng SHU
Author Information
1. 复旦大学基础医学院药理学系 上海 200032
- Keywords:
glioma;
m6A methylation;
RNA modification;
double-stranded RNA;
PKR
- From:
Fudan University Journal of Medical Sciences
2024;51(3):295-305
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of radiotherapy simulant Zeocin induced double-stranded RNA(dsRNA)on double-stranded RNA-dependent protein kinase(PKR)activation and explore its molecular mechanism in inhibiting the growth and migration of malignant gliomas.Methods We employed scratch assays,colony formation assays,and CCK8 assays to assess the impact of Zeocin on glioma growth and migration inhibition.Western blot and RT-qPCR were employed to measure the expression levels of methyl-modifying enzymes in glioma cells.The J2 antibody was used to detect endogenous dsRNA in malignant glioma cells treated with Zeocin.Western blot was used to assess the phosphorylation levels of PKR and eukaryotic initiating factor 2α(eIF2α).Results Zeocin significantly inhibited growth and migration of glioma cells;Zeocin treatment induced the production of endogenous dsRNA in malignant glioma cells;as the concentration of Zeocin increased,phosphorylated PKR and eIF2αprotein level also significantly increased;Zeocin downregulated the total m6A level of glioma cells in a dose-dependent manner;Zeocin selectively downregulated the protein level of methylase METTL14;Zeocin had no effect on mRNA levels of m6A modifying enzymes.Conclusion Zeocin probably triggered more dsRNA by downregulating the m6A level of RNA in malignant glioma cells,which in turn activated the PKR/eIF2α pathway,ultimately leading to tumor growth inhibition.
