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Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630662/ https://www.ncbi.nlm.nih.gov/pubmed/38028194 http://dx.doi.org/10.1016/j.omtn.2023.102058 |
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author | Yin, Jiaqi Ding, Na Yu, Jiaxin Wang, Zishan Fu, Limei Li, Yongsheng Li, Xia Xu, Juan |
author_facet | Yin, Jiaqi Ding, Na Yu, Jiaxin Wang, Zishan Fu, Limei Li, Yongsheng Li, Xia Xu, Juan |
author_sort | Yin, Jiaqi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10630662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-106306622023-10-16 Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity Yin, Jiaqi Ding, Na Yu, Jiaxin Wang, Zishan Fu, Limei Li, Yongsheng Li, Xia Xu, Juan Mol Ther Nucleic Acids Original Article 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. American Society of Gene & Cell Therapy 2023-10-16 /pmc/articles/PMC10630662/ /pubmed/38028194 http://dx.doi.org/10.1016/j.omtn.2023.102058 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Yin, Jiaqi Ding, Na Yu, Jiaxin Wang, Zishan Fu, Limei Li, Yongsheng Li, Xia Xu, Juan Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity |
title | Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity |
title_full | Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity |
title_fullStr | Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity |
title_full_unstemmed | Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity |
title_short | Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity |
title_sort | systematic analysis of dna methylation-mediated tf dysregulation on lncrnas reveals critical roles in tumor immunity |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630662/ https://www.ncbi.nlm.nih.gov/pubmed/38028194 http://dx.doi.org/10.1016/j.omtn.2023.102058 |
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