LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2'-O-methylation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37980347.
- Also identified by DOI 10.1038/s41467-023-43113-5 and PMC identifier 10657414.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>'</sup>-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.
Medical subject headings
- RNA, Long Noncoding
- Brain Neoplasms
- Glioma
- Glioblastoma