Methyladenosine Modification in RNAs: From Regulatory Roles to Therapeutic Implications in Cancer

Qu, Xiaolin; Zhang, Yongqiu; Sang, Xianzheng; Ren, Dianxu; Zhao, Hong; Wong, Stephen T.C.

doi:10.3390/cancers14133195

Cited by 9 publications

(7 citation statements)

References 167 publications

(244 reference statements)

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“…Genetic and epigenetic alterations have been closely associated with tumorigenesis. RNA methylation modifications play a role in many processes, like cell differentiation and development [16,[26][27][28]. DNA methylation plays an important role in the occurrence and progression of cancers [29,30].…”

Section: Discussionmentioning

confidence: 99%

A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase (<i>DLAT</i>) as a novel prognostic biomarker in pan-cancer and glioma

ZHOU,

YU,

et al. 2024

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Background: Dihydrolipoamide S-acetyltransferase (DLAT) is a subunit of the pyruvate dehydrogenase complex (PDC), a rate-limiting enzyme complex, that can participate in either glycolysis or the tricarboxylic acid cycle (TCA). However, the pathogenesis is not fully understood. We aimed to perform a more systematic and comprehensive analysis of DLAT in the occurrence and progression of tumors, and to investigate its function in patients' prognosis and immunotherapy. Methods: The differential expression, diagnosis, prognosis, genetic and epigenetic alterations, tumor microenvironment, stemness, immune infiltration cells, function enrichment, single-cell analysis, and drug response across cancers were conducted based on multiple computational tools. Additionally, we validated its carcinogenic effect and possible mechanism in glioma cells. Results: We exhibited that DLAT expression was increased in most tumors, especially in glioma, and affected the survival of tumor patients. DLAT was related to RNA modification genes, DNA methylation, immune infiltration, and immune infiltration cells, including CD4+ T cells, CD8+ T cells, Tregs, and cancer-associated fibroblasts. Single-cell analysis displayed that DLAT might regulate cancer by mediating angiogenesis, inflammation, and stemness. Enrichment analysis revealed that DLAT might take part in the cell cycle pathway. Increased expression of DLAT leads tumor cells to be more resistant to many kinds of compounds, including PI3Kβ inhibitors, PKC inhibitors, HSP90 inhibitors, and MEK inhibitors. In addition, glioma cells with DLAT silence inhibited proliferation, migration, and invasion ability, and promoted cell apoptosis. Conclusion: We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors, and its possible functions and mechanisms. DLAT is a potential diagnostic, prognostic, and immunotherapeutic biomarker for cancer patients.

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Section: Discussionmentioning

confidence: 99%

A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase (<i>DLAT</i>) as a novel prognostic biomarker in pan-cancer and glioma

ZHOU,

YU,

et al. 2024

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“…One of the main reasons is that m 1 A modification is rare in RNA. 66 Previous technical limitations were mainly based on the normal physiological effects of m 1 A modifications in cells under cell culture conditions. However, with the progress of high-throughput sequencing technology, the role of m 1 A in different types of tumors, such as hepatocellular carcinoma, 67 glioma 68 , 69 and bladder cancer 70 has been gradually clarified.…”

Section: The Function Of Rna Modifications From Transcription To Tran...mentioning

confidence: 99%

RNA Modifications Meet Tumors

Yang¹,

Zhang²,

Xia³

et al. 2022

CMAR

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RNA modifications occur through the whole process of gene expression regulation, including transcription, translation, and post-translational processes. They are closely associated with gene expression, RNA stability, and cell cycle. RNA modifications in tumor cells play a vital role in tumor development and metastasis, changes in the tumor microenvironment, drug resistance in tumors, construction of tumor cell-cell “internet”, etc. Several types of RNA modifications have been identified to date and have various effects on the biological characteristics of different tumors. In this review, we discussed the function of RNA modifications, including N 6 -methyladenine (m 6 A), 5-methylcytosine (m 5 C), N 7 -methyladenosine (m 7 G), N 1 -methyladenosine (m 1 A), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I), in the microenvironment and therapy of solid and liquid tumors.

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“…According to different functions, m 6 A modification proteins can be divided into methyltransferase (writer), demethylase (eraser), and m 6 A-binding protein (reader). For example, methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and WT1 proteins can induce RNA methylation, while alkB homolog 5 (ALKBH5) functions as an RNA demethylase that can erase RNA methylation and reverse methylation (13). Moreover, YTH domain family (YTHDF) 1-3 and YTH domain-containing family (YTHDC) 1-2 are m 6 A-binding proteins that recognize m 6 A methylation modification of RNA and thus affect the fate of mRNA (14).…”

Section: A Methylation Modification-related Proteinsmentioning

confidence: 99%

An overview of the effects and mechanisms of m6 A methylation on innate immune cells in sepsis

Qian

Cao

2022

Front. Immunol.

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IntroductionSepsis is a severe clinical syndrome caused by dysregulated systemic inflammatory responses to infection. Methylation modification, as a crucial mechanism of RNA functional modification, can manipulate the immunophenotype and functional activity of immune cells to participate in sepsis progression. This study aims to explore the mechanism of N6-methyladenosine (m6A) methylation modification in immune cell-mediated sepsis through keyword search.MethodsLiterature retrieval.Results and DiscussionLiterature retrieval reveals that m6A methylation is implicated in sepsis-induced lung injury and myocardial injury,as well as sepsis-related encephalopathy. Furthermore, it is found that m6A methylation can regulate sepsis by inhibiting the chemotaxis of neutrophils and the formation of neutrophil extracellular traps and suppressing macrophage phagocytosis, thereby playing a role in sepsis.

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Methyladenosine Modification in RNAs: From Regulatory Roles to Therapeutic Implications in Cancer

Cited by 9 publications

References 167 publications

A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase (<i>DLAT</i>) as a novel prognostic biomarker in pan-cancer and glioma

A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase (<i>DLAT</i>) as a novel prognostic biomarker in pan-cancer and glioma

RNA Modifications Meet Tumors

An overview of the effects and mechanisms of m6 A methylation on innate immune cells in sepsis

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