LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2'-O-methylation.
Lihui LiuZiyang LiuQinghua LiuWei WuPeng LinXing LiuYuechuan ZhangDongpeng WangBriana C PragerRyan N GimpleJichuan YuWeixi ZhaoQiulian WuWei ZhangErzhong WuXiaomin ChenJianjun LuoJeremy N RichQi XieTao JiangRunsheng ChenPublished in: Nature communications (2023)
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.
Keyphrases
- stem cells
- genome wide
- dna methylation
- binding protein
- long non coding rna
- small cell lung cancer
- endothelial cells
- transcription factor
- long noncoding rna
- gene expression
- cell cycle
- tyrosine kinase
- mesenchymal stem cells
- epidermal growth factor receptor
- cancer therapy
- cell therapy
- young adults
- pi k akt
- amino acid
- pluripotent stem cells