The role of N6-methyladenosine mRNA in the tumor microenvironment

Li, Min; Zha, Xuan; Wang, Shengjun

doi:10.1016/j.bbcan.2021.188522

Cited by 97 publications

(92 citation statements)

References 145 publications

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“…Further, the TGF-β pathway suppresses the effect of CD8 + T cells by regulating regulatory T cells (Tregs). Mechanistically, previous study showed that m6A modification directly or indirectly involved in the regulation of cancerrelated pathways such as proliferation, apoptosis, invasion and metastasis, and metabolic reprogramming (Li et al, 2021). Some investigators have found that YTHDF1 regulated the translation of FZD7 which is a key Wnt receptor by an m6Adependent manner (Pi et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

Wang

Zhou

et al. 2021

Front. Cell Dev. Biol.

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Background: Immunotherapy elicits durable responses in many tumors. Nevertheless, the positive response to immunotherapy always depends on the dynamic interactions between the tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of immunotherapy in hepatocellular carcinoma (HCC) has achieved limited success. The ectopic modification of N6-methyladenosine (m6A) is a common feature in multiple tumors. However, the relationship between m6A modification with HCC clinical features, prognosis, immune cell infiltration, and immunotherapy efficacy remains unclear.Materials and Methods: Here, we comprehensively evaluated m6A modification clusters based on 22 m6A regulators and systematically explored the relationship between m6A modification with tumor progression, prognosis, and immune cell infiltration characteristics. The m6Ascore was calculated by principal component analysis to quantify the m6A modifications of individual patients. Key regulators involved in immunoregulation in HCC were identified using immunohistochemistry and immunofluorescence.Results: Three distinct m6A modification clusters were identified. The m6A clusters were significantly associated with clinical features, prognosis, and immune cell infiltration. The three clusters were highly consistent with the three tumor immune phenotypes, i.e., immune-excluded, immune-inflamed, and immune-desert. Comprehensive bioinformatics analysis revealed that high m6Ascore was closely associated with tumor progression, poor prognosis, and immunotherapy non-response. m6A regulators were dysregulated in HCC tissues. Hence, they play a role as predictors of poor prognosis. Tissue microarray demonstrated that overexpressed YTHDF1 was associated with low CD3+ and CD8+ T cell infiltration in HCC.Conclusion: Our findings demonstrate that m6A modification patterns play a crucial role in the tumor immune microenvironment and the prognosis of HCC. High YTHDF1 expression is closely associated with low CD3+ and CD8+ T cell infiltration in HCC.

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Section: Discussionmentioning

confidence: 99%

m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

Wang

Zhou

et al. 2021

Front. Cell Dev. Biol.

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“…In recent studies, many researchers have found that HDACIs also have significant effects on host immunosuppressive cells. As MDSCs are important immunosuppressive cells in the tumor microenvironment ( 32 ), it is worth investigating the regulatory effects of HDACIs these cells.…”

Section: Introductionmentioning

confidence: 99%

Regulatory Effects of Histone Deacetylase Inhibitors on Myeloid-Derived Suppressor Cells

et al. 2021

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Histone deacetylase inhibitors (HDACIs) are antitumor drugs that are being developed for use in clinical settings. HDACIs enhance histone or nonhistone acetylation and promote gene transcription via epigenetic regulation. Importantly, these drugs have cytotoxic or cytostatic properties and can directly inhibit tumor cells. However, how HDACIs regulate immunocytes in the tumor microenvironment, such as myeloid-derived suppressor cells (MDSCs), has yet to be elucidated. In this review, we summarize the effects of different HDACIs on the immunosuppressive function and expansion of MDSCs based on the findings of relevant studies.

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“…Recent research reports have uncovered the relationship between m6A modification and tumor microenvironment (TME) (15), immune response (16,17), and chemotherapy (18). m6A mRNA is crucial in the development or function of immune cells.…”

Section: Introductionmentioning

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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The role of N6-methyladenosine mRNA in the tumor microenvironment

Cited by 97 publications

References 145 publications

m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

Regulatory Effects of Histone Deacetylase Inhibitors on Myeloid-Derived Suppressor Cells

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

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