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

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...

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Detalles Bibliográficos
Autores principales: Liu, Lihui, Liu, Ziyang, Liu, Qinghua, Wu, Wei, Lin, Peng, Liu, Xing, Zhang, Yuechuan, Wang, Dongpeng, Prager, Briana C., Gimple, Ryan C., Yu, Jichuan, Zhao, Weixi, Wu, Qiulian, Zhang, Wei, Wu, Erzhong, Chen, Xiaomin, Luo, Jianjun, Rich, Jeremy N., Xie, Qi, Jiang, Tao, Chen, Runsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10657414/
https://www.ncbi.nlm.nih.gov/pubmed/37980347
http://dx.doi.org/10.1038/s41467-023-43113-5
Descripción
Sumario: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.

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