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; Runsheng Chen

doi:10.1038/s41467-023-43113-5

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

Nat Commun. 2023 Nov 18;14(1):7526. doi: 10.1038/s41467-023-43113-5.

Authors

Lihui Liu^#¹, Ziyang Liu^#^{1

2}, Qinghua Liu^#¹, Wei Wu^#¹, Peng Lin^#^{3

4}, Xing Liu^#⁵, Yuechuan Zhang⁶, Dongpeng Wang¹, Briana C Prager^{7

8}, Ryan C Gimple⁷, Jichuan Yu^{3

4}, Weixi Zhao^{3

4}, Qiulian Wu⁹, Wei Zhang¹⁰, Erzhong Wu¹, Xiaomin Chen¹, Jianjun Luo¹, Jeremy N Rich¹¹, Qi Xie^{12

13}, Tao Jiang^{14

15}, Runsheng Chen^{16

17}

Affiliations

¹ Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
² University of Chinese Academy of Sciences, 100049, Beijing, China.
³ Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, 310024, Hangzhou, China.
⁴ Westlake Laboratory of Life Sciences and Biomedicine, 310024, Hangzhou, China.
⁵ Beijing Neurosurgical Institute, 100050, Beijing, China.
⁶ Department of Department of Orthopedics, Peking Union Medical College Hospital, 100730, Beijing, China.
⁷ Department of Pathology, Case Western Reserve University, Cleveland, 44106, USA.
⁸ Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, 44195, USA.
⁹ Hillman Cancer Center and Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, 15261, USA.
¹⁰ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 100050, Beijing, China.
¹¹ Hillman Cancer Center and Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, 15261, USA. drjeremyrich@gmail.com.
¹² Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, 310024, Hangzhou, China. xieqi@westlake.edu.cn.
¹³ Westlake Laboratory of Life Sciences and Biomedicine, 310024, Hangzhou, China. xieqi@westlake.edu.cn.
¹⁴ Beijing Neurosurgical Institute, 100050, Beijing, China. taojiang1964@163.com.
¹⁵ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 100050, Beijing, China. taojiang1964@163.com.
¹⁶ Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China. rschen@ibp.ac.cn.
¹⁷ University of Chinese Academy of Sciences, 100049, Beijing, China. rschen@ibp.ac.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / genetics
Brain Neoplasms* / metabolism
Cell Line, Tumor
Glioblastoma* / genetics
Glioblastoma* / metabolism
Glioma* / genetics
Glioma* / metabolism
Humans
Methylation
Neoplastic Stem Cells / metabolism
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Ribonucleoproteins, Small Nucleolar / metabolism

Substances

RNA, Long Noncoding
Ribonucleoproteins, Small Nucleolar