Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity

Jiaqi Yin; Na Ding; Jiaxin Yu; Zishan Wang; Limei Fu; Yongsheng Li; Xia Li; Juan Xu

Molecular Therapy: Nucleic Acids (Dec 2023)

Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity

Jiaqi Yin,
Na Ding,
Jiaxin Yu,
Zishan Wang,
Limei Fu,
Yongsheng Li,
Xia Li,
Juan Xu

Affiliations

Jiaqi Yin: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
Na Ding: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
Jiaxin Yu: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
Zishan Wang: Department of Genetics and Genomic Sciences, Center for Transformative Disease Modeling, Tisch Cancer Institute, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Limei Fu: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
Yongsheng Li: School of Interdisciplinary Medicine and Engineering, Harbin Medical University, Harbin 150081, China; Corresponding author: Yongsheng Li, School of Interdisciplinary Medicine and Engineering, Harbin Medical University, Harbin 150081, China.
Xia Li: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China; Corresponding author: Xia Li, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Juan Xu: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China; Corresponding author: Juan Xu, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

Journal volume & issue: Vol. 34
p. 102058

Abstract

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Emerging evidence suggests that DNA methylation affects transcriptional regulation and expression perturbations of long non-coding RNAs (lncRNAs) in cancer. However, a comprehensive investigation into the transcriptional control of DNA methylation-mediated dysregulation of transcription factors (TFs) on lncRNAs has been lacking. Here, we integrated the transcriptome, methylome, and regulatome across 21 human cancers and systematically identified the transcriptional regulation of DNA methylation-mediated TF dysregulations (DMTDs) on lncRNAs. Our findings reveal that TF regulation of lncRNAs is significantly impacted by DNA methylation. Comparative analysis of DMTDs on mRNAs revealed a conserved pattern of TFs involvement. Pan-cancer Methylation TFs (MethTFs) and Methylation LncRNAs (MethLncRNAs) were identified, and were found to be closely associated with cancer hallmarks and clinical features. In-depth analysis of co-expressed mRNAs with pan-cancer MethLncRNAs unveiled frequent disruptions in cancer immunity, particularly in the context of inflammatory response. Furthermore, we identified five immune-related network modules that contribute to immune cell infiltration in cancer. Immune-related subtypes were subsequently classified, characterized by high levels of immune cell infiltration, expression of immunomodulatory genes, and relevant immune cytolytic activity score, major histocompatibility complex score, response to chemotherapy, and prognosis. Our findings provide valuable insights into cancer immunity from the epigenetic and transcriptional regulation perspective.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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