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

doi:10.1111/jcmm.16961

Cited by 26 publications

(14 citation statements)

References 60 publications

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“…These studies suggest that the expression changes of key genes related to m6A regulators function may lead to phenotypic alteration. In addition, our previous research has shown that m6A regulator–mediated RNA methylation modification was involved in asthma ( Sun et al, 2021 ). In this study, we will continue to investigate the relationship between m6A and asthma; we systematically evaluated the transcriptome-wide m6A methylome and m6A-modified genes in asthma by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome-Wide m6A Methylome and m6A-Modified Gene Analysis in Asthma

Sun

Shen

et al. 2022

Front. Cell Dev. Biol.

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N6-methyladenosine (m6A) modification is one of the most prevalent RNA modification forms and is an important posttranscriptional mechanism for regulating genes. In previous research, we found that m6A regulator–mediated RNA methylation modification was involved in asthma; however, the specific modified genes are not clear. In this study, we systematically evaluated the transcriptome-wide m6A methylome and m6A-modified genes in asthma. Here, we performed two high-throughput sequencing methods, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and RNA sequencing (RNA-seq) to identify key genes with m6A modification in asthma. Through difference analysis, we found that 416 methylation peaks were significantly upregulated and 152 methylation peaks were significantly downregulated, and it was mainly distributed in 3′ UTR. Furthermore, compared with the control group, there were 2,505 significantly upregulated genes and 4,715 significantly downregulated genes in the asthma group. Next, through a combined analysis of transcriptome and differential peaks, 14 differentially expressed genes related to RNA methylation modification were screened. Finally, through 87 health controls and 411 asthma cases from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) program, we verified three m6A-modified key genes (BCL11A, MATK, and CD300A) and found that they were mainly distributed in exons and enriched in 3' UTR. Our findings suggested that intervening in m6A-modified genes may provide a new idea for the treatment of asthma.

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Section: Introductionmentioning

confidence: 99%

Transcriptome-Wide m6A Methylome and m6A-Modified Gene Analysis in Asthma

Sun

Shen

et al. 2022

Front. Cell Dev. Biol.

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“…The role of YTHDF2 in preventing excessive inflammatory responses is a potential therapeutic target for inflammatory diseases ( Yu et al, 2019 ). One study classified severe asthma into three m6A modification patterns, which can achieve precise treatment according to the characteristics of the immune microenvironment ( Sun et al, 2021 ). Lynall et al (2020) stratified patients with depression according to their leukocyte subsets and found that the inflammatory depression subgroup had more severe depressive symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies suggested a fundamental role for m6A modifications in the tumor immune microenvironment ( Han et al, 2019 ; Zhang et al, 2020 ). More recent studies revealed that m6A plays a similarly crucial role in the immune microenvironment of periodontitis ( Zhang et al, 2021 ) and severe asthma ( Sun et al, 2021 ). For multifaceted diseases such as depression, which is influenced by multiple factors such as genetic susceptibility and the inflammatory response, early diagnosis and treatment are critical.…”

Section: Introductionmentioning

confidence: 99%

m6A Regulator-Mediated RNA Methylation Modification Patterns are Involved in the Pathogenesis and Immune Microenvironment of Depression

Wang

Yang

et al. 2022

Front. Genet.

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Depression is a genetical disease characterized by neuroinflammatory symptoms and is difficult to diagnose and treat effectively. Recently, modification of N6-methyladenosine (m6A) at the gene level was shown to be closely related to immune regulation. This study was conducted to explore the effect of m6A modifications on the occurrence of depression and composition of the immune microenvironment. We downloaded gene expression profile data of healthy and depressed rats from the Gene Expression Omnibus. We described the overall expression of m6A regulators in animal models of depression and constructed risk and clinical prediction models using training and validation sets. Bioinformatics analysis was performed using gene ontology functions, gene set enrichment analysis, gene set variation analysis, weighted gene co-expression network analysis, and protein-protein interaction networks. We used CIBERSORT to identify immune-infiltrating cells in depression and perform correlation analysis. We then constructed two molecular subtypes of depression and assessed the correlation between the key genes and molecular subtypes. Through differential gene analysis of m6A regulators in depressed rats, we identified seven m6A regulators that were significantly upregulated in depressed rats and successfully constructed a clinical prediction model. Gene Ontology functional annotation showed that the m6A regulators enriched differentially expressed genes in biological processes, such as the regulation of mRNA metabolic processes. Further, 12 hub genes were selected from the protein-protein interaction network. Immune cell infiltration analysis showed that levels of inflammatory cells, such as CD4 T cells, were significantly increased in depressed rats and were significantly correlated with the depression hub genes. Depression was divided into two subtypes, and the correlation between hub genes and these two subtypes was clarified. We described the effect of m6A modification on the pathogenesis of depression, focusing on the role of inflammatory infiltration.

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“…Many severe asthma patients show abnormal YTHDF3 and YTHDC1 expression. YTHDF3 is responsible for shifting the immune microenvironment, resulting in increased eosinophil infiltration (D. Sun et al, 2021). A frequent consequence of lung transplantation is lung ischemia‐reperfusion injury (LIRI).…”

Section: Role Of Yth Domain Family (Ythdf) Proteins In Human Physiolo...mentioning

confidence: 99%

Modulation of gene expression by YTH domain family (YTHDF) proteins in human physiology and pathology

Kisan

Chhabra

2022

Journal Cellular Physiology

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

Cited by 26 publications

References 60 publications

Transcriptome-Wide m6A Methylome and m6A-Modified Gene Analysis in Asthma

Transcriptome-Wide m6A Methylome and m6A-Modified Gene Analysis in Asthma

m6A Regulator-Mediated RNA Methylation Modification Patterns are Involved in the Pathogenesis and Immune Microenvironment of Depression

Modulation of gene expression by YTH domain family (YTHDF) proteins in human physiology and pathology

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