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m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma

N6‐methyladenosine (m6A) modification is one of the most prevalent RNA modification forms of eukaryotic mRNA and is an important post‐transcriptional mechanism for regulating genes. However, the role of m6A modification in the regulation of severe asthma has never been reported. Thus, we aimed to in...

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Autores principales: Sun, Deyang, Yang, Huan, Fan, Liming, Shen, Fenglin, Wang, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572790/
https://www.ncbi.nlm.nih.gov/pubmed/34647423
http://dx.doi.org/10.1111/jcmm.16961
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author Sun, Deyang
Yang, Huan
Fan, Liming
Shen, Fenglin
Wang, Zhen
author_facet Sun, Deyang
Yang, Huan
Fan, Liming
Shen, Fenglin
Wang, Zhen
author_sort Sun, Deyang
collection PubMed
description N6‐methyladenosine (m6A) modification is one of the most prevalent RNA modification forms of eukaryotic mRNA and is an important post‐transcriptional mechanism for regulating genes. However, the role of m6A modification in the regulation of severe asthma has never been reported. Thus, we aimed to investigate the m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma. In this study, 87 healthy controls and 344 severe asthma cases from the U‐BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) programme were used to systematically evaluate the m6A modification patterns mediated by 27 m6A regulators and to investigate the effects of m6A modification on immune microenvironment characteristics. We found that 16 m6A regulators were abnormal and identified two key m6A regulators (YTHDF3 and YTHDC1) and three m6A modification patterns. The study of infiltration characteristics of immune microenvironment found that pattern 2 had more infiltrating immune cells and more active immune response. Besides, it was found that the eosinophils which are very important for severe asthma were affected by YTHDF3 and EIF3B. We also verified key m6A regulators with merip‐seq and found that they were mainly distributed in exons and enriched in 3′UTR. In conclusion, our findings suggested that m6A modification plays a key role in severe asthma, and may be able to guide the future strategy of immunotherapy.
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spelling pubmed-85727902021-11-10 m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma Sun, Deyang Yang, Huan Fan, Liming Shen, Fenglin Wang, Zhen J Cell Mol Med Original Articles N6‐methyladenosine (m6A) modification is one of the most prevalent RNA modification forms of eukaryotic mRNA and is an important post‐transcriptional mechanism for regulating genes. However, the role of m6A modification in the regulation of severe asthma has never been reported. Thus, we aimed to investigate the m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma. In this study, 87 healthy controls and 344 severe asthma cases from the U‐BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) programme were used to systematically evaluate the m6A modification patterns mediated by 27 m6A regulators and to investigate the effects of m6A modification on immune microenvironment characteristics. We found that 16 m6A regulators were abnormal and identified two key m6A regulators (YTHDF3 and YTHDC1) and three m6A modification patterns. The study of infiltration characteristics of immune microenvironment found that pattern 2 had more infiltrating immune cells and more active immune response. Besides, it was found that the eosinophils which are very important for severe asthma were affected by YTHDF3 and EIF3B. We also verified key m6A regulators with merip‐seq and found that they were mainly distributed in exons and enriched in 3′UTR. In conclusion, our findings suggested that m6A modification plays a key role in severe asthma, and may be able to guide the future strategy of immunotherapy. John Wiley and Sons Inc. 2021-10-14 2021-11 /pmc/articles/PMC8572790/ /pubmed/34647423 http://dx.doi.org/10.1111/jcmm.16961 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Sun, Deyang
Yang, Huan
Fan, Liming
Shen, Fenglin
Wang, Zhen
m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma
title m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma
title_full m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma
title_fullStr m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma
title_full_unstemmed m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma
title_short m6A regulator‐mediated RNA methylation modification patterns and immune microenvironment infiltration characterization in severe asthma
title_sort m6a regulator‐mediated rna methylation modification patterns and immune microenvironment infiltration characterization in severe asthma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572790/
https://www.ncbi.nlm.nih.gov/pubmed/34647423
http://dx.doi.org/10.1111/jcmm.16961
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