LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2'-O-methylation.

Abstract

Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal and tumorigenicity through control of rRNA 2'-O-methylation. INHEG induces the interaction between SUMO2 E3 ligase TAF15 and NOP58, a core component of snoRNP that guides rRNA methylation, to regulate NOP58 sumoylation and accelerate the C/D box snoRNP assembly. INHEG activation enhances rRNA 2'-O-methylation, thereby increasing the expression of oncogenic proteins including EGFR, IGF1R, CDK6 and PDGFRB in glioma cells. Taken together, this study identifies a lncRNA that connects snoRNP-guided rRNA 2'-O-methylation to upregulated protein translation in GSCs, supporting an axis for potential therapeutic targeting of gliomas.

• Authors: Lihui Liu, Ziyang Liu, Qinghua Liu, Wei Wu, Peng Lin, Xing Liu, Yuechuan Zhang, Dongpeng Wang, Briana C Prager, Ryan C Gimple, Jichuan Yu, Weixi Zhao, Qiulian Wu, Wei Zhang, Erzhong Wu, Xiaomin Chen, Jianjun Luo, Jeremy N Rich, Qi Xie, Tao Jiang, Runsheng Chen
• Journal: Nature communications (Nat Commun) Vol. 14 Issue 1 Pg. 7526 (11 18 2023) ISSN: 2041-1723 [Electronic] England
• PMID: 37980347 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• RNA, Long Noncoding
• Ribonucleoproteins, Small Nucleolar

Topics

• Humans
• RNA, Long Noncoding (genetics, metabolism)
• Methylation
• Brain Neoplasms (genetics, metabolism)
• Ribonucleoproteins, Small Nucleolar (metabolism)
• Neoplastic Stem Cells (metabolism)
• Glioma (genetics, metabolism)
• Glioblastoma (genetics, metabolism)
• Cell Line, Tumor