N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand

Ogawa, Akiko; Nagiri, Chisae; Shihoya, Wataru; Inoue, Asuka; Kawakami, Kouki; Hiratsuka, Suzune; Aoki, Junken; Ito, Yasuhiro; Suzuki, Tsutomu; Inoue, Toshihiro; Nureki, Osamu; Tanihara, Hidenobu; Tomizawa, Kazuhito; Wei, Fan Yan

doi:10.1016/j.molcel.2020.12.038

Cited by 33 publications

(46 citation statements)

References 83 publications

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“…m 6 A methyltransferases are known as ‘writers’ and they include methyltransferase-like protein (METTL)-3, METTL4, and Wilms tumor 1-associating protein (WTAP) [ 9 ]. Meanwhile, m 6 A demethyltransferases are known as ‘erasers’ and they include AlkB Homolog 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) [ 10 ]. m 6 A recognition proteins are known as ‘readers’ and they include the YTH domain-containing protein (YTHDC)-1, YTHDC2, YTH m 6 A RNA-binding protein (YTHDF)-1, YTHDF2, and YTHDF3 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

et al. 2022

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Glioma is one of the leading causes of tumor-related deaths worldwide, but its potential mechanism remains unclear. This study aimed to explore the biological role and potential mechanism of argininosuccinate synthase 1 (ASS1) in glioma. The relative expression levels of ASS1 in glioma specimens and cell lines were calculated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The biological functions of ASS1 were demonstrated using the 5-ethynyl-2ʹ-deoxyuridine (EdU) assay, transwell assay, and in vivo experiments. In addition, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanism of ASS1 in glioma. ASS1 expression levels were found to be downregulated in glioma specimens and cell lines. Functionally, we confirmed that ASS1 inhibited glioma cell proliferation, migration, invasion, and growth both. Furthermore, we found that ASS1 was a target of N(6)-adenosine-methyltransferase-14 (METTL14)-mediated N 6 -methyladenosine (m 6 A) modification. Overexpression of METTL14 markedly elevated ASS1 mRNA m 6 A modification and suppressed ASS1 mRNA expression. We also revealed that METTL14-mediated ASS1 mRNA degradation relied on the YTH m6A RNA-binding protein 2 (YTHDF2)-dependent pathway. We confirmed that decreased ASS1 expression promoted the cell proliferation, migration, and invasion in glioma, and that the METTL14/ASS1/YTHDF2 regulatory axis may be an effective therapeutic target for glioma.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

et al. 2022

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“…Posttranscriptional RNA modification is an essential process for translation. An estimated approximately 150 posttranscriptional RNA modifications have been proven in all species (Ogawa et al, 2021). Among those modifications, m 6 A is the most popular among eukaryotic mRNAs and long noncoding RNAs (Kwok et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma

Feng

Wang

et al. 2021

Front. Mol. Biosci.

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Background: The purpose of our research was to establish a gene signature and determine the prognostic value of m6A methylation regulators in cutaneous melanoma and WTAP as a protective gene in cutaneous melanoma prognosis, we also evaluated gene mutations in cutaneous melanoma.Methods: We downloaded the RNA-seq transcriptome data and the clinical information for cutaneous melanoma patients from the GTEx and TCGA databases. Consensus clustering analysis was applied to divide the samples into two groups. Then the least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature, and we use external and internal datasets to verify its predictive value. We further searched the cBioPortal tools to detect genomic alterations and WTAP mutations. Finally, WTAP was further identified as a prognostic factor, and the related mechanisms mediated by WTAP were predicted by gene set enrichment analysis (GSEA). Experimental validations and have been further carried out.Results: Notably, m6A RNA methylation regulators play significant roles in tumorigenesis and development. In total, we selected three subtypes of cutaneous melanoma according to consensus clustering of the m6A RNA methylation regulators, and the stage of cutaneous melanoma was proven to be related to the subtypes. The Cox regression and LASSO analyses built a risk signature including ELF3, ZC3H13 and WTAP. The prognostic value of the risk signature in internal and external datasets have been proven then. The whole-genome and selected gene WTAP mutations were further explored. WTAP as a single prognostic factor was also explored and found to serve as an independent protective prognostic factor.Conclusions: Our study constructed a stable risk signature composed of m6A RNA methylation regulators in cutaneous melanoma. Moreover, WTAP was identified as a valuable prognostic factor and potential molecular target for cutaneous melanoma treatment.

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“…However, only a small part of these RNAs can be translated into proteins. During translation process, the RNA modification after transcription is a critical step, and approximately 150 post-transcriptional RNA modifications have been demonstrated across species ( Motorin and Helm, 2011 ; Ogawa et al, 2021 ). Among these modifications, N6-methyladenosine (m 6 A) is the most common among eukaryotic mRNAs and long non-coding RNAs.…”

Section: Discussionmentioning

confidence: 99%

Immune Infiltrates of m6A RNA Methylation-Related lncRNAs and Identification of PD-L1 in Patients With Primary Head and Neck Squamous Cell Carcinoma

Feng

Gao

Feng

2021

Front. Cell Dev. Biol.

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Background: The purpose of this study was to determine the association between m6A-modified lncRNAs, immune infiltration, and PD-L1 expression in patients with primary head and neck squamous cell carcinoma (HNSCC) and the prognostic value of m6A RNA methylation-related lncRNAs in HNSCC.Methods: We downloaded the RNA-seq transcriptome data and the clinical information for HNSCC from the TCGA databases and used consensus clustering analysis to divide the samples into two groups. To identify a risk signature, least absolute shrinkage and selection operator (LASSO) analyses were conducted. the association between m6A-modified lncRNAs, immune infiltration, and PD-L1 expression were detected by using the R packages. What is more, we used cBioPortal tools to identify genomic alterations and PD-L1 mutations and Gene set enrichment analysis (GSEA) was utilized to predict downstream access of two clusters.Results: Notably, lncRNAs play significant roles in tumorigenesis and development. In total, we identified two subtypes of HNSCC according to consensus clustering of the m6A RNA methylation-related lncRNAs, and the T, grade and age were proven to be related to the subtypes. The Cox regression and LASSO analyses identified a risk signature including GRHL3-AS1, AL121845.4, AC116914.2, AL513190.1. The prognostic value of the risk signature was then proven. The selected gene PD-L1 mutations and the immune infiltration in both groups were further explored.Conclusion: Collectively, our study elucidated the important role of m6A RNA methylation- related lncRNAs in tumor microenvironment of HNSCC. The proposed m6A RNA methylation- related lncRNAs might serve as crucial mediators of tumor microenvironment of HNSCC, representing promising therapeutic targets in improving immunotherapeutic efficacy.

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N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand

Cited by 33 publications

References 83 publications

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

RETRACTED ARTICLE: N(6)-adenosine-methyltransferase-14 promotes glioma tumorigenesis by repressing argininosuccinate synthase 1 expression in an m6A-dependent manner

Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma

Immune Infiltrates of m6A RNA Methylation-Related lncRNAs and Identification of PD-L1 in Patients With Primary Head and Neck Squamous Cell Carcinoma

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