Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas

Xu, Dahua; Cao, Meng; Wang, Bo; Bi, Xiaoman; Zhang, Haiying; Wu, Deng; Zhang, Chunrui; Xu, Jiankai; Xu, Zhizhou; Zheng, Dehua; Chen, Liyang; Li, Peihu; Wang, Hong; Liu, Yan; Jiang, Hongyan; Li, Kongning

doi:10.7150/thno.79874

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Nanotheranostics 2024; 8(3): 380-400. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(3): 344-379. [Abstract] [Full text] [PDF] [PubMed] [PMC]

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Theranostics 2023; 13(5):1490-1505. doi:10.7150/thno.79874 This issue Cite

Research Paper

Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas

Dahua Xu^1,2#, Meng Cao^2#, Bo Wang^1#, Xiaoman Bi^2#, Haiying Zhang³, Deng Wu⁴, Chunrui Zhang⁵, Jiankai Xu⁶, Zhizhou Xu², Dehua Zheng², Liyang Chen², Peihu Li², Hong Wang², Yan Liu^3✉, Hongyan Jiang^1✉, Kongning Li^1,2✉

1. Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, China.
2. Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Hainan Medical University, Haikou, 571199, China
3. Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Pharmaceutical, Hainan Medical University, Haikou, 571199, China
4. School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, 999077, Hong Kong
5. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100020, China
6. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
^# These authors contributed equally to this work

Citation:

Xu D, Cao M, Wang B, Bi X, Zhang H, Wu D, Zhang C, Xu J, Xu Z, Zheng D, Chen L, Li P, Wang H, Liu Y, Jiang H, Li K. Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas. Theranostics 2023; 13(5):1490-1505. doi:10.7150/thno.79874. https://www.thno.org/v13p1490.htm

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Abstract

Background: Glioblastomas are the most common and malignant central nervous system (CNS) tumors that occupied a highly heterogeneous tumor microenvironment (TIME). Long noncoding RNAs (lncRNAs), whose expression can be modified by DNA methylation, are emerging as critical regulators in the immune system. However, knowledge about the epigenetic changes in lncRNAs and their contribution to the immune heterogeneity of glioma is still lacking.

Methods: In this study, we integrated paired methylome and transcriptome datasets of glioblastomas and identified 2 robust immune subtypes based on lncRNA methylation features. The immune characteristics of glioma subtypes were compared. Furthermore, immune-related lncRNAs were identified and their relationships with immune evasion were evaluated.

Results: Glioma immunophenotypes exhibited distinct immune-related characteristics as well as clinical and epigenetic features. 149 epigenetically regulated (ER) lncRNAs were recognized that possessed inverse variation in epigenetic and transcriptional levels between glioma subtypes. Immune-related lncRNAs were further identified through the investigation of their correlation with immune cell infiltrations and immune-related pathways. In particular, the 'Hot' glioma subtype with higher immunoactivity while a worse survival outcome was found to character immune evasion features. We finally prioritized candidate ER lncRNAs associated with immune evasion markers and response to glioma immunotherapy. Among them, CD109-AS1 and LINC02447 were validated as novel immunoevasive biomarkers for glioma through in vitro experiments.

Conclusion: In summary, our study systematically reveals the crosstalk among DNA methylation, lncRNA, and immune regulation in glioblastomas, and will facilitate the development of epigenetic immunotherapy approaches.

Keywords: glioblastomas, DNA methylation, long non-coding RNAs, cancer subtypes, immune microenvironment

Citation styles

APA

Xu, D., Cao, M., Wang, B., Bi, X., Zhang, H., Wu, D., Zhang, C., Xu, J., Xu, Z., Zheng, D., Chen, L., Li, P., Wang, H., Liu, Y., Jiang, H., Li, K. (2023). Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas. Theranostics, 13(5), 1490-1505. https://doi.org/10.7150/thno.79874.

ACS

Xu, D.; Cao, M.; Wang, B.; Bi, X.; Zhang, H.; Wu, D.; Zhang, C.; Xu, J.; Xu, Z.; Zheng, D.; Chen, L.; Li, P.; Wang, H.; Liu, Y.; Jiang, H.; Li, K. Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas. Theranostics 2023, 13 (5), 1490-1505. DOI: 10.7150/thno.79874.

NLM

CSE

Xu D, Cao M, Wang B, Bi X, Zhang H, Wu D, Zhang C, Xu J, Xu Z, Zheng D, Chen L, Li P, Wang H, Liu Y, Jiang H, Li K. 2023. Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas. Theranostics. 13(5):1490-1505.

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