N6-methyladenosine (m6A) RNA modification in cancer stem cells

Ma, Zhonghua; Ji, Jiafu

doi:10.1002/stem.3279

Cited by 77 publications

(56 citation statements)

References 71 publications

(218 reference statements)

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“…As a current highly promising RNA modification, m6A methylation has been experimentally confirmed to play a key role in the development of various cancers ( Vu et al, 2017 ), while the study of m6A methylation provides a new perspective for GBM treatment. m6A modifications have been shown to potentially affect the formation of a variety of peripheral tumor microenvironments (TME), be involved in cancer stem cells (CSCs) generation and maintenance, the control of cancer progression, and treatment resistance ( Ma and Ji, 2020 ). Previous studies have confirmed that GBM is more heterogeneous than other peripheral tumors, suggesting that multiple factors may influence developmental plasticity and immune checkpoint blockade therapy in GBM, possibly including the TME, RNA modifications, and stem cell phenotype ( Malta et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of m6A Regulator-Mediated Methylation Modification and Tumor Microenvironment Infiltration in Glioblastoma Multiforme

Wang

Cao

Zhong

et al. 2022

Front. Cell Dev. Biol.

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N6-methyladenosine (m6A) RNA methylation is an emerging epigenetic modification in recent years and epigenetic regulation of the immune response has been demonstrated, but the potential role of m6A modification in GBM tumor microenvironment (TME) cell infiltration and stemness remain unknown. The m6A modification patterns of 310 GBM samples were comprehensively evaluated based on 21 m6A regulators, and we systematically correlated these modification patterns with TME cell infiltration characteristics and stemness characteristics. Construction of m6Ascore to quantify the m6A modification patterns of individual GBM samples using a principal component analysis algorithm. We identified two distinct patterns of m6A modification. The infiltration characteristics of TME cells in these two patterns were highly consistent with the immunophenotype of the GBM, including the immune activation differentiation pattern and the immune desert dedifferentiation pattern. We also identified two modes of regulation of immunity and stemness by m6A methylation. Stromal activation and lack of effective immune infiltration were observed in the high m6Ascore subtype. Pan-cancer analysis results illustrate a significant correlation between m6AScore and tumor clinical outcome, immune infiltration, and stemness. Our work reveals that m6A modifications play an important role in the development of TME and stemness diversity and complexity. Patients with a low m6AScore showed significant therapeutic advantages and clinical benefits. Assessing the m6A modification pattern of individual tumors will help enhance our knowledge of TME infiltration and stemness characteristics, contribute to the development of immunotherapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

The Role of m6A Regulator-Mediated Methylation Modification and Tumor Microenvironment Infiltration in Glioblastoma Multiforme

Wang

Cao

Zhong

et al. 2022

Front. Cell Dev. Biol.

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“…Moreover, LLPS is involved in modulating RNA N6 methyladenosine (m6A) (Yu et al, 2019), which had been found to have a key role in tumor occurrence and development (Chen et al, 2020;Ma and Ji, 2020). In addition, however, the role of LLPS in digestive system tumors is still largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…LLPS could also affect transcriptional regulation, maintaining genomic stability and signal transduction, which may contribute to the occurrence and progression of tumors ( Peng et al, 2021 ). Moreover, LLPS is involved in modulating RNA N6 methyladenosine (m6A) ( Yu et al, 2019 ), which had been found to have a key role in tumor occurrence and development ( Chen et al, 2020 ; Ma and Ji, 2020 ). In addition, however, the role of LLPS in digestive system tumors is still largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of Molecular Characterization and Clinical Relevance of Liquid–Liquid Phase Separation Regulators in Digestive System Neoplasms

Zhang

Feng

et al. 2022

Front. Cell Dev. Biol.

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Background: The role of liquid–liquid phase separation (LLPS) in cancer has also attracted more and more attention, which is found to affect transcriptional regulation, maintaining genomic stability and signal transduction, and contribute to the occurrence and progression of tumors. However, the role of LLPS in digestive system tumors is still largely unknown.Results: Here, we characterized the expression profiles of LLPS regulators in 3 digestive tract tumor types such as COAD, STAD, and ESCA with The Cancer Genome Atlas (TCGA) data. Our results for the first time showed that LLPS regulatory factors, such as Brd4, FBN1, and TP53, were frequently mutated in all types of digestive system tumors. Variant allele frequency (VAF) and APOBEC analysis demonstrated that genetic alterations of LLPS regulators were related to the progression of digestive system neoplasms (DSNs), such as TP53, NPHS1, TNRC6B, ITSN1, TNPO1, PML, AR, BRD4, DLG4, and PTPN1. KM plotter analysis showed that the mutation status of LLPS regulators was significantly related to the overall survival (OS) time of DSNs, indicating that they may contribute to the progression of DSN. The expression analysis of LLPS regulatory factors showed that a variety of LLPS regulatory factors were significantly dysregulated in digestive system tumors, such as SYN2 and MAPT. It is worth noting that we first found that LLPS regulatory factors were significantly correlated with tumor immune infiltration of B cells, CD4+ T cells, and CD8+ T cells in digestive system tumors. Bioinformatics analysis showed that the LLPS regulators’ expression was closely related to multiple signaling, including the ErbB signaling pathway and T-cell receptor signaling pathway. Finally, several LLPS signatures were constructed and had a strong prognostic stratification ability in different digestive gland tumors. Finally, the results demonstrated the LLPS regulators’ signature score was significantly positively related to the infiltration levels of CD4+ T cells, neutrophil cells, macrophage cells, and CD8+ T cells.Conclusion: Our study for the first time showed the potential roles of LLPS regulators in carcinogenesis and provide novel insights to identify novel biomarkers for the prediction of immune therapy and prognosis of DSNs.

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“…M6A modification is involved in all mRNA metabolic processes, including maturation, transport, splicing, translation, and degradation ( Song et al, 2020 ; Li et al, 2021b Li et al, 2021c ; Lou et al, 2021 ). M6A RNA methylation exerts critical biological functions in mammals, such as tissue development, circadian rhythms, DNA damage responses, gender identification, and tumor occurrence and development ( Xu et al, 2020a ; Li et al, 2020 ; Ma and Ji 2020 ; Gu et al, 2021b ; Wu and Wang 2021 ). In this review, we discuss the potential mechanisms of m6A methylation-related regulators in BC initiation and development.…”

Section: Introductionmentioning

confidence: 99%

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Liu

2022

Front. Genet.

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N6-methyladenosine (m6A) is a dynamic, reversible post-transcriptional modification, and the most common internal modification of eukaryotic messenger RNA (mRNA). Considerable evidence now shows that m6A alters gene expression, thereby regulating cell self-renewal, differentiation, invasion, and apoptotic processes. M6A methylation disorders are directly related to abnormal RNA metabolism, which may lead to tumor formation. M6A methyltransferase is the dominant catalyst during m6A modification; it removes m6A demethylase, promotes recognition by m6A binding proteins, and regulates mRNA metabolic processes. Bladder cancer (BC) is a urinary system malignant tumor, with complex etiology and high incidence rates. A well-differentiated or moderately differentiated pathological type at initial diagnosis accounts for most patients with BC. For differentiated superficial bladder urothelial carcinoma, the prognosis is normally good after surgery. However, due to poor epithelial cell differentiation, BC urothelial cell proliferation and infiltration may lead to invasive or metastatic BC, which lowers the 5-years survival rate and significantly affects clinical treatments in elderly patients. Here, we review the latest progress in m6A RNA methylation research and investigate its regulation on BC occurrence and development.

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N6-methyladenosine (m6A) RNA modification in cancer stem cells

Cited by 77 publications

References 71 publications

The Role of m6A Regulator-Mediated Methylation Modification and Tumor Microenvironment Infiltration in Glioblastoma Multiforme

The Role of m6A Regulator-Mediated Methylation Modification and Tumor Microenvironment Infiltration in Glioblastoma Multiforme

Systematic Analysis of Molecular Characterization and Clinical Relevance of Liquid–Liquid Phase Separation Regulators in Digestive System Neoplasms

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

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