Emerging role of RNA modification N6-methyladenosine in immune evasion

Lou, Xin; Wang, Sheng; Wei, Yaqing; Sun, Jinjin

doi:10.1038/s41419-021-03585-z

Cited by 44 publications

(35 citation statements)

References 73 publications

(55 reference statements)

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“…Compelling evidence has shown that m6A modification is involved in the TME, tumor progression, and therapy responses (29)(30)(31). Although many studies have demonstrated the epigenetic regulatory role of m6A regulatory factor in tumor development and progression, the tumor promotion and tumor inhibition mediated by integrated m6A RNA methylation regulators factor have not been comprehensively understood.…”

Section: Discussionmentioning

confidence: 99%

Identification of an N6-methyladenosine (m6A)-related signature associated with clinical prognosis, immune response, and chemotherapy in primary glioblastomas

Cai¹,

Zhang²,

Liu³

et al. 2021

Ann Transl Med

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Background: N6-methyladenosine (m6A) RNA methylation regulators play crucial role in tumorigenicity and progression. However, their biological significance in primary glioblastomas (GBM) has not been fully elucidated.Methods: In the present study, we evaluated the 22 m6A RNA regulators using the integrated data of primary GBM samples from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. The different m6A modification patterns and m6A-related gene signature in primary GBM were distinguished by using principal component analysis. Single-sample gene set enrichment analysis was introduced to assess the relative level of immune infiltration. Gene set variation analysis was performed to calculate the enrichment score of the signaling pathways for different clusters. An m6A scoring scheme was established to evaluate the m6A modification pattern in individual tumors in order to predict prognosis and evaluate tumor microenvironment (TME) cell infiltration, immune response, and chemotherapy effect in primary GBM.Results: Two distinct m6A modification subgroups associated with different clinical features and biological pathways were identified among the 371 primary GBM. Based on 132 prognostic m6A phenotype-related differentially expressed genes (DEGs) between 2 m6A cluster subgroups, an m6A scoring model was constructed to assess the m6A modification pattern in individual tumors. The high-m6A score group was associated with better prognosis and immune response and worse chemotherapy effect. Conclusions:The findings of the present study indicate the potential role of m6A modification in primary GBM, which will help enhance our understanding of TME characteristics, predict clinical prognosis, and provide important insight into effective immunotherapy and chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Identification of an N6-methyladenosine (m6A)-related signature associated with clinical prognosis, immune response, and chemotherapy in primary glioblastomas

Cai¹,

Zhang²,

Liu³

et al. 2021

Ann Transl Med

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“…In addition, it should be noted that a number of biological processes and pathways associated with immune response were identi ed. While extensive literature reports have demonstrated that N6-methyladenosine plays important role in immune evasion and immune response [40,41], there have been few reports about the relationship between m 5 C-related RNA modi cations and immune response, suggesting that further research is required.…”

Section: Discussionmentioning

confidence: 99%

Gene Signature And Prognostic Values of m5C-Related Regulators In Colon Adenocarcinoma

Huang

Jiang

et al. 2021

Preprint

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Objectives: The purpose of this study was to investigate the role of 13 m5C-related regulators in colon adenocarcinoma (COAD) and determine their prognostic value.Main Methods: Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) datasets. The expression of m5C-related regulators were analyzed with clinicopathological characteristics and alterations within m5C-related regulators. Subsequently, different subtypes of patients with COAD were identified. Then, the prognostic value of m5C-related regulators in COAD were confirmed via univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The prognostic value of risk scores was evaluated using the Kaplan-Meier method, receiver operating characteristic (ROC) curves, and univariate and multivariate regression analyses. Additionally, Gene Set Enrichment Analysisc (GSEA), Kyoto Encyclopedia of Genes and Genomes c (KEGG) pathways, and Gene Ontologyc (GO) analysis were performed for biological functional analysis.Results: m5C-related regulators were found to be differentially expressed in COAD with different clinicopathological features. We observed a high alteration frequency in these genes, which were significantly correlated with their mRNA expression levels. Two clusters with different prognostic features were identified. Based on two independent prognostic m5C-related regulators (NSUN6 and ALYREF), a risk signature with good predictive significance was constructed. Univariate and multivariate Cox regression analyses suggested that the risk score was an independent prognostic factor. Biological processes and pathways associated with cancer, immune response, and RNA processing were identified.Conclusion: We revealed the genetic signatures and prognostic values of m5C-related regulators in COAD. Together, this has improved our understanding of m5C RNA modification and provided novel insights to identify predictive biomarkers and develop molecular targeted therapy for COAD.

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“…The transcription factor Foxp3, a marker molecule of Treg cells, is regulated by the Suppressor of cytokine signaling (SOCS) family and activates STAT5 ( Tong et al, 2018 ). It has been reported that in a mouse model that has been constructed with METTL3 deletion, elevated expression of the SOCS gene compared to controls inhibited IL2-STAT5 signaling pathway and maintained the inhibitory function of Treg ( Lou et al, 2021 ). Secondly, in hepatocellular carcinoma, METTL3 overexpression then inhibited the expression of suppressor of cytokine signaling factor 2 (SOCS2) through an m6A-YTHDF2-dependent mechanism, which ultimately promoted tumor growth ( Tuncel and Kalkan, 2019 ).…”

Section: M6a Rna Modification Affects the Infiltration Characteristics Of Cancer Cells In Tumor Microenvironmentmentioning

confidence: 99%

Effect, Mechanism, and Applications of Coding/Non-coding RNA m6A Modification in Tumor Microenvironment

Chen

Guo

et al. 2021

Front. Cell Dev. Biol.

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The tumor microenvironment (TME), which includes immune cells, fibroblasts, and other components, is the site of tumor cell growth and metastasis and significantly impacts tumor development. Among them, N6-methyladenosine RNA modifications (m6A RNA modifications) are the most abundant internal modifications in coding and non-coding RNAs, which can significantly influence the cancer process and have potential as biomarkers and potential therapeutic targets for tumor therapy. This manuscript reviews the role of m6A RNA modifications in TME and their application in tumor therapy. To some extent, an in-depth understanding of the relationship between TME and m6A RNA modifications will provide new approaches and ideas for future cancer therapy.

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Emerging role of RNA modification N6-methyladenosine in immune evasion

Cited by 44 publications

References 73 publications

Identification of an N6-methyladenosine (m6A)-related signature associated with clinical prognosis, immune response, and chemotherapy in primary glioblastomas

Identification of an N6-methyladenosine (m6A)-related signature associated with clinical prognosis, immune response, and chemotherapy in primary glioblastomas

Gene Signature And Prognostic Values of m5C-Related Regulators In Colon Adenocarcinoma

Effect, Mechanism, and Applications of Coding/Non-coding RNA m6A Modification in Tumor Microenvironment

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