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Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome

N6-methyladenosine (m6A) RNA modification is a new epigenetic regulation mechanism on eukaryotic mRNA. Few autoimmune diseases focused on the role of m6A in their pathogenies, and m6A modulation in the pathological process of primary Sjögren’s syndrome (pSS) is still unknown. In this work, three mic...

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Autores principales: Cheng, Linlin, Li, Haolong, Zhan, Haoting, Liu, Yongmei, Li, Xiaomeng, Huang, Yuan, Wang, Li, Zhang, Fengchun, Li, Yongzhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530814/
https://www.ncbi.nlm.nih.gov/pubmed/36203590
http://dx.doi.org/10.3389/fimmu.2022.949206
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author Cheng, Linlin
Li, Haolong
Zhan, Haoting
Liu, Yongmei
Li, Xiaomeng
Huang, Yuan
Wang, Li
Zhang, Fengchun
Li, Yongzhe
author_facet Cheng, Linlin
Li, Haolong
Zhan, Haoting
Liu, Yongmei
Li, Xiaomeng
Huang, Yuan
Wang, Li
Zhang, Fengchun
Li, Yongzhe
author_sort Cheng, Linlin
collection PubMed
description N6-methyladenosine (m6A) RNA modification is a new epigenetic regulation mechanism on eukaryotic mRNA. Few autoimmune diseases focused on the role of m6A in their pathogenies, and m6A modulation in the pathological process of primary Sjögren’s syndrome (pSS) is still unknown. In this work, three microarray datasets of pSS patients were downloaded from the GEO database: datasets #1 and #2 from the whole peripheral blood (PB) samples, dataset #3 from the labial salivary gland tissue samples, as well as a PB cohort collected from our hospital. Six differentially expressed m6A regulators were identified by comparing the PB dataset #1 of pSS and healthy controls using the Wilcox test and logistic regression analysis. Among them, four (ALKBH5, RBMX, RBM15B, and YTHDF1) were confirmed as down-regulated in PB dataset #2 and in our PB cohort by RT-PCR, and four (ALKBH5, METTL3, RBM15B, and YTHDF1) were confirmed as down-regulated in the dataset #3 of the labial gland tissue. In addition, discrepantly expressed m6A regulators accompanied by diverse immunocytes, including dendritic cells (DCs), T cells, and CD56dim natural killer cells, and among the regulators, ALKBH5 and METTL3 were comprehensively linked with the infiltrated immune cells. Notably, the most enriched autophagy mechanism mediated by m6A was observed in pSS using functional annotation analysis. Ten hub genes were identified using a protein-protein interaction network, and their expression in PB dataset #2 and the expression of three genes (PIK3CA, STAT1, and MAPK3) in the labial gland tissue dataset #3 were confirmed. Our study provides evidence that m6A methylation is widely involved in the immune infiltration and autophagy of pSS, thus contributing to the pathogenesis of this disease and potentially representing a novel therapeutic target.
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spelling pubmed-95308142022-10-05 Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome Cheng, Linlin Li, Haolong Zhan, Haoting Liu, Yongmei Li, Xiaomeng Huang, Yuan Wang, Li Zhang, Fengchun Li, Yongzhe Front Immunol Immunology N6-methyladenosine (m6A) RNA modification is a new epigenetic regulation mechanism on eukaryotic mRNA. Few autoimmune diseases focused on the role of m6A in their pathogenies, and m6A modulation in the pathological process of primary Sjögren’s syndrome (pSS) is still unknown. In this work, three microarray datasets of pSS patients were downloaded from the GEO database: datasets #1 and #2 from the whole peripheral blood (PB) samples, dataset #3 from the labial salivary gland tissue samples, as well as a PB cohort collected from our hospital. Six differentially expressed m6A regulators were identified by comparing the PB dataset #1 of pSS and healthy controls using the Wilcox test and logistic regression analysis. Among them, four (ALKBH5, RBMX, RBM15B, and YTHDF1) were confirmed as down-regulated in PB dataset #2 and in our PB cohort by RT-PCR, and four (ALKBH5, METTL3, RBM15B, and YTHDF1) were confirmed as down-regulated in the dataset #3 of the labial gland tissue. In addition, discrepantly expressed m6A regulators accompanied by diverse immunocytes, including dendritic cells (DCs), T cells, and CD56dim natural killer cells, and among the regulators, ALKBH5 and METTL3 were comprehensively linked with the infiltrated immune cells. Notably, the most enriched autophagy mechanism mediated by m6A was observed in pSS using functional annotation analysis. Ten hub genes were identified using a protein-protein interaction network, and their expression in PB dataset #2 and the expression of three genes (PIK3CA, STAT1, and MAPK3) in the labial gland tissue dataset #3 were confirmed. Our study provides evidence that m6A methylation is widely involved in the immune infiltration and autophagy of pSS, thus contributing to the pathogenesis of this disease and potentially representing a novel therapeutic target. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9530814/ /pubmed/36203590 http://dx.doi.org/10.3389/fimmu.2022.949206 Text en Copyright © 2022 Cheng, Li, Zhan, Liu, Li, Huang, Wang, Zhang and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Cheng, Linlin
Li, Haolong
Zhan, Haoting
Liu, Yongmei
Li, Xiaomeng
Huang, Yuan
Wang, Li
Zhang, Fengchun
Li, Yongzhe
Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome
title Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome
title_full Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome
title_fullStr Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome
title_full_unstemmed Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome
title_short Alterations of m6A RNA methylation regulators contribute to autophagy and immune infiltration in primary Sjögren’s syndrome
title_sort alterations of m6a rna methylation regulators contribute to autophagy and immune infiltration in primary sjögren’s syndrome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530814/
https://www.ncbi.nlm.nih.gov/pubmed/36203590
http://dx.doi.org/10.3389/fimmu.2022.949206
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