m6A regulator-mediated methylation modification patterns and characteristics of immunity and stemness in low-grade glioma

Du, Jianyang; Ji, Hang; Ma, Shuai; Jin, Jiaqi; Mi, Shan; Hou, Kezuo; Dong, Jiawei; Wang, Fang; Zhang, Chaochao; Li, Yuan; Hu, Shaoshan

doi:10.1093/bib/bbab013

Cited by 66 publications

(52 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NAT10, the only confirmed regulator of mRNA acetyltransferase, shows remarkable correlation with most cancers in immune infiltration. However, as in the case of m6A RNA methylation regulators which change the levels of m6A in immune infiltration of cancers ( 35 , 36 ), the details of the molecular mechanism of NAT10 involved in the acetylation of mRNA are not clear. We tried to screen out the targeting NAT10-binging proteins and the NAT10-correlated genes for in-depth pathway enrichment analyses.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

Yang

Zhang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

BackgroundNAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.MethodsIn this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA2, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA2.ResultsCompared with normal tissues, NAT10 showed higher expression in most cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.ConclusionNAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

“…As in the case of m6A RNA methylation regulators, it has been reported that m6A regulators play independent role of immune infiltration in several types of cancers ( 35 , 36 , 39 ). In this study, we first presented the evidence of the potential correlation between NAT10, RNA acetylation regulator, with immune infiltration.…”

Section: Discussionmentioning

confidence: 95%

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

Yang

Zhang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Bo Zhang and colleagues demonstrated that modification of m6A methylation is involved in the regulation of the microenvironment of gastric cancer, and has a guiding role in immunotherapy ( 46 ). Jianyang Du and coworkers revealed that m6A regulators had different modification patterns and characteristics of immunity in low-grade glioma ( 47 ). Most studies have focused on m6A modification, the overall TME characterization mediated by mt-rRNA modification and its regulators is not recognized.…”

Section: Discussionmentioning

confidence: 99%

Human Mitochondrial Ribosomal RNA Modification-Based Classification Contributes to Discriminate the Prognosis and Immunotherapy Response of Glioma Patients

Wang

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

BackgroundEpigenetic regulations of the tumor microenvironment (TME) and immunotherapy have been investigated in recent years. Nevertheless, the potential value of mitochondrial ribosomal RNA (mt-rRNA) modification in regulation of the TME and immunotherapy remains unknown.MethodsWe comprehensively investigated the mt-rRNA-modification patterns in glioma patients based on nine regulators of mt-rRNA. Subsequently, these modification patterns were correlated systematically with immunologic characteristics and immunotherapy. An “mt-rRNA predictor” was constructed and validated in multiple publicly available cohorts to provide guidance for prognosis prediction and immunotherapy of glioma patients.ResultsTwo distinct patterns of mt-rRNA modification were determined based on the evidence that nine regulators of mt-rRNA correlated significantly with most clinicopathologic characteristics, immunomodulators, TME, immune-checkpoint blockers (ICBs), and prognosis. Patients with mt-rRNA subtype II presented significantly poorer overall survival/progression-free survival (OS/PFS), but higher tumor mutational burden (TMB), more somatic mutations, and copy number variation (CNV). These two mt-rRNA subtypes had distinct TME patterns and responses to ICB therapy. An mt-rRNA predictor was constructed and validated in four glioma cohorts. The subtype with high mt-rRNA score, characterized by increased TMB, infiltration of immune cells, and activation of immunity, suggested an immune-activated phenotype, and was also linked to greater sensitivity to immunotherapy using anti-programmed cell death protein 1 (PD-1) but resistance to temozolomide.ConclusionsRegulators of mt-rRNA modification have indispensable roles in the complexity and diversity of the TME and prognosis. This novel classification based on patterns of mt-rRNA modification could provide an effective prognostic predictor and guide more appropriate immunotherapy/chemotherapy strategies for glioma patients.

show abstract

“…Furthermore, high ALKBH5 levels in colon cancer indicates poor prognosis ( Huang et al, 2021 ). In addition, numerous studies used the m 6 Ascore to investigate the potential clinical implications of m 6 A RNA modification patterns in cancer ( Zhang B. et al, 2020 ; Du et al, 2021 ; Shen et al, 2021a ; Xu et al, 2021b ). For example, Zhang C. et al (2020) indicated that the m 6 Ascore can act as an independent prognostic biomarker in gastric cancer.…”

Section: Potential Clinical Implications Of M 6 a Rna Modification In Cancersmentioning

confidence: 99%

N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors

Zhan

Zhang

Zhu

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Immunotherapy is a novel clinical approach that has shown clinical efficacy in multiple cancers. However, only a fraction of patients respond well to immunotherapy. Immuno-oncological studies have identified the type of tumors that are sensitive to immunotherapy, the so-called hot tumors, while unresponsive tumors, known as “cold tumors,” have the potential to turn into hot ones. Therefore, the mechanisms underlying cold tumor formation must be elucidated, and efforts should be made to turn cold tumors into hot tumors. N6-methyladenosine (m6A) RNA modification affects the maturation and function of immune cells by controlling mRNA immunogenicity and innate immune components in the tumor microenvironment (TME), suggesting its predominant role in the development of tumors and its potential use as a target to improve cancer immunotherapy. In this review, we first describe the TME, cold and hot tumors, and m6A RNA modification. Then, we focus on the role of m6A RNA modification in cold tumor formation and regulation. Finally, we discuss the potential clinical implications and immunotherapeutic approaches of m6A RNA modification in cancer patients. In conclusion, m6A RNA modification is involved in cold tumor formation by regulating immunity, tumor-cell-intrinsic pathways, soluble inhibitory mediators in the TME, increasing metabolic competition, and affecting the tumor mutational burden. Furthermore, m6A RNA modification regulators may potentially be used as diagnostic and prognostic biomarkers for different types of cancer. In addition, targeting m6A RNA modification may sensitize cancers to immunotherapy, making it a promising immunotherapeutic approach for turning cold tumors into hot ones.

show abstract

m6A regulator-mediated methylation modification patterns and characteristics of immunity and stemness in low-grade glioma

Cited by 66 publications

References 51 publications

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

Human Mitochondrial Ribosomal RNA Modification-Based Classification Contributes to Discriminate the Prognosis and Immunotherapy Response of Glioma Patients

N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors

Contact Info

Product

Resources

About