Dissemin is shutting down on January 1st, 2025

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Nature Research, Nature Communications, 1(14), 2023

DOI: 10.1038/s41467-023-43113-5

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

Journal article published in 2023 by Lihui Liu ORCID, Ziyang Liu, Qinghua Liu, Wei Wu, Peng Lin, Xing Liu, Yuechuan Zhang ORCID, Dongpeng Wang, Briana C. Prager, Ryan C. Gimple ORCID, Jichuan Yu, Weixi Zhao, Qiulian Wu, Wei Zhang, Erzhong Wu and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractGlioblastoma (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.