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

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 () and Runsheng Chen ()
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Lihui Liu: Chinese Academy of Sciences
Ziyang Liu: Chinese Academy of Sciences
Qinghua Liu: Chinese Academy of Sciences
Wei Wu: Chinese Academy of Sciences
Peng Lin: Westlake University
Xing Liu: Beijing Neurosurgical Institute
Yuechuan Zhang: Peking Union Medical College Hospital
Dongpeng Wang: Chinese Academy of Sciences
Briana C. Prager: Case Western Reserve University
Ryan C. Gimple: Case Western Reserve University
Jichuan Yu: Westlake University
Weixi Zhao: Westlake University
Qiulian Wu: University of Pittsburgh Medical Center
Wei Zhang: Capital Medical University
Erzhong Wu: Chinese Academy of Sciences
Xiaomin Chen: Chinese Academy of Sciences
Jianjun Luo: Chinese Academy of Sciences
Jeremy N. Rich: University of Pittsburgh Medical Center
Qi Xie: Westlake University
Tao Jiang: Beijing Neurosurgical Institute
Runsheng Chen: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43113-5

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