Methyltransferase-like proteins in cancer biology and potential therapeutic targeting

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 2, 2023

Abstract RNA modification has recently become a significant process of gene regulation, and the methyltransferase-like (METTL) family proteins plays critical role in modification, methylating various types RNAs, including mRNA, tRNA, microRNA, rRNA, mitochondrial RNAs. METTL consist unique seven-beta-strand domain, which binds to methyl donor SAM catalyze transfer. The most typical member METTL3/METTL14 forms methyltransferase complex involved N 6-methyladenosine (m6A) RNA, regulating tumor proliferation, metastasis invasion, immunotherapy resistance, metabolic reprogramming cells. METTL1, METTL4, METTL5, METTL16 have also been identified some regulatory ability tumorigenesis, rest members rely on their activity for methylation different nucleotides, proteins, small molecules, regulate translation affect processes such as cell differentiation development. Herein, we summarize literature METTLs last three years elucidate roles human cancers provide theoretical basis future use potential therapeutic targets.

Language: Английский

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m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 1, 2023

Abstract N6-methyladenosine (m 6 A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m A writers, erasers, and readers, modulation involved myriad physiological pathological processes. Extensive studies have demonstrated diverse tumours, with effects on tumorigenesis, metastasis, resistance. Recent evidence has revealed an emerging role of tumour immunoregulation, divergent patterns been microenvironment. To depict regulatory immune microenvironment (TIME) its effect evasion, this review focuses TIME, which characterized hypoxia, metabolic reprogramming, acidity, immunosuppression, outlines A-regulated TIME evasion under stimuli. Furthermore, anti-tumour cells are summarized.

Language: Английский

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Molecular mechanisms in MASLD/MASH-related HCC

Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 13, 2024

Liver cancer is the third leading cause of cancer-related deaths and ranks as sixth most prevalent type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, its more severe manifestation, NASH steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% population. The increased prevalence disease MASH parallel to increasing rates obesity-associated diseases, including 2 diabetes, insulin resistance, fatty diseases. can progress MASH-related HCC (MASH-HCC) in about 2% cases each year, influenced by various factors such genetic mutations, carcinogen exposure, immune microenvironment, microbiome. MASH-HCC exhibits distinct molecular characteristics compared other causes affects both men women equally. management early intermediate-stage typically involves surgery locoregional therapies, while advanced treated with systemic anti-angiogenic therapies checkpoint inhibitors. In this comprehensive review, we consolidate previous research findings also providing current insights into intricate processes underlying development. We delve MASH-HCC-associated variations somatic progression models, multiomics analysis, immunological microenvironmental impacts, discuss targeted/combined overcome evasion biomarkers recognize treatment responders. By furthering our comprehension mechanisms MASH-HCC, goal catalyze advancement potent strategies, ultimately enhanced patient outcomes.

Language: Английский

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RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 27, 2024

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding pathophysiology, inspiring development therapeutics. As a crucial component epigenetics at post-transcription level, RNA modification significantly determines fates, further affecting various biological processes cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells different stages immunological contexts. In this review, we characterize distribution features, modifying mechanisms functions 8 modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively most studied types. Then regulatory roles these diverse health disease contexts comprehensively described, categorized as glucose, lipid, amino acid, mitochondrial metabolism. And highlight regulation modifications immunometabolism, influencing responses. Above all, provide thorough discussion about clinical implications metabolism-targeted therapy immunotherapy, progression modification-targeted agents, its potential RNA-targeted Eventually, give legitimate perspectives for future researches field from methodological requirements, mechanistic insights, to therapeutic applications.

Language: Английский

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The role of RNA methylation in tumor immunity and its potential in immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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Critical roles and clinical perspectives of RNA methylation in cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: May 1, 2024

Abstract RNA modification, especially methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all modifications. It plays significant role in metabolism, affecting processing, stability, translation, thereby modulating gene expression cell essential proliferation, survival, metastasis. Increasing studies have revealed the disruption metabolism mediated by methylation has been implicated various aspects cancer particularly metabolic reprogramming immunity. This profound implications tumor growth, metastasis, therapy response. Herein, we elucidate fundamental characteristics their impact on expression. We highlight intricate relationship between reprogramming, immunity, using well‐characterized phenomenon as framework to discuss methylation's specific roles mechanisms progression. Furthermore, explore potential targeting regulators novel approach therapy. By underscoring complex which contributes this review provides foundation developing new prognostic markers therapeutic strategies aimed at treatment.

Language: Английский

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METTL3: a multifunctional regulator in diseases

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Language: Английский

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IGF2BP3 is an essential N6-methyladenosine biotarget for suppressing ferroptosis in lung adenocarcinoma cells

Materials Today Bio, Journal Year: 2022, Volume and Issue: 17, P. 100503 - 100503

Published: Nov. 24, 2022

A lack of promising targets leads to poor prognosis in patients with lung adenocarcinoma (LUAD). Therefore, it is urgent identify novel therapeutic targets. The importance the N6-methyladenosine (m6A) RNA modification has been demonstrated various types tumors; however, knowledge m6A-related proteins LUAD still limited. Here, we found that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), an m6A reader protein, highly expressed and associated prognosis. IGF2BP3 desensitizes ferroptosis (a new form regulated cell death) a manner dependent on its reading domain capacity m6A-methylated mRNAs encoding anti-ferroptotic factors, including but not limited glutathione peroxidase 4 (GPX4), solute carrier family member (SLC3A2), acyl-CoA synthetase long chain (ACSL3), ferritin heavy 1 (FTH1). After overexpression, expression levels stabilities these factors were successfully sustained. Notably, significant correlations between SLC3A2, ACSL3, revealed clinical specimens, further establishing essential role desensitizing ferroptosis. Inducing gradually accepted as alternative strategy treat tumors. Thus, could be potential target for future development biomaterial-associated anti-tumor drugs.

Language: Английский

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The role of RNA m6A methylation in lipid metabolism

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 8, 2022

The m6A methylation is the most numerous modification of mRNA in mammals, coordinated by RNA methyltransferases, demethylases, and binding proteins. They change level their specific manner. has a significant impact on lipid metabolic regulation. “writer” METTL3/METTL14 “eraser” FTO can promote accumulation lipids various cells affecting decomposition synthesis lipids. “reader” YTHDF recognizes sites regulates target genes’ translation. Due to this function that metabolism, plays pivotal role diseases makes it great potential for therapy.

Language: Английский

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Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102963 - 102963

Published: Nov. 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious that affects 30 % of the global population and poses significant risk to human health. However, date, no safe, effective appropriate treatment modalities are available. In recent years, ferroptosis has emerged as mode cell death been found play key regulatory role in development NAFLD. this study, we arbutin (ARB), natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits onset ameliorates high-fat diet-induced NAFLD vivo vitro. Using reverse docking, identified demethylase fat mass obesity-related protein (FTO) potential target ARB. Subsequent mechanistic studies revealed ARB plays controlling methylation SLC7A11 gene through inhibition FTO. addition, demonstrated could alleviate Our findings identify FTO/SLC7A11 axis therapeutic for Specifically, show alleviates by acting on pathway inhibit ferroptosis.

Language: Английский

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