The roles and implications of RNA m6A modification in cancer

Nature Reviews Clinical Oncology, Год журнала: 2023, Номер 20(8), С. 507 - 526

Опубликована: Май 23, 2023

Язык: Английский

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Methyltransferase-like proteins in cancer biology and potential therapeutic targeting

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Авг. 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.

Язык: Английский

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

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Март 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.

Язык: Английский

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N6-methyladenosine reader YTHDF family in biological processes: Structures, roles, and mechanisms

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 14, 2023

As the most abundant and conserved internal modification in eukaryote RNAs, N6-methyladenosine (m 6 A) is involved a wide range of physiological pathological processes. The YT521-B homology (YTH) domain-containing family proteins (YTHDFs), including YTHDF1, YTHDF2, YTHDF3, are class cytoplasmic m A-binding defined by vertebrate YTH domain, exert extensive functions regulating RNA destiny. Distinct expression patterns YTHDF specific cell types or developmental stages result prominent differences multiple biological processes, such as embryonic development, stem fate, fat metabolism, neuromodulation, cardiovascular effect, infection, immunity, tumorigenesis. mediates tumor proliferation, metastasis, drug resistance, possesses potential predictive therapeutic biomarkers. Here, we mainly summary structures, roles, mechanisms especially cancers, well their current limitations future considerations. This will provide novel angles for deciphering A regulation system.

Язык: Английский

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Therapeutic m⁶A Eraser ALKBH5 mRNA-Loaded Exosome–Liposome Hybrid Nanoparticles Inhibit Progression of Colorectal Cancer in Preclinical Tumor Models

ACS Nano, Год журнала: 2023, Номер 17(12), С. 11838 - 11854

Опубликована: Июнь 13, 2023

Although therapeutic targets have been developed for colorectal cancer (CRC) therapy, the effects are not ideal and survival rate CRC patients remains poor. Therefore, it is crucial to recognize a specific target develop an efficacious delivery system therapy. Herein, we demonstrate that reduced ALKBH5 mediates aberrant m6A modification tumor progression in CRC. Mechanically, histone deacetylase 2-mediated H3K27 deacetylation inhibits transcription CRC, whereas ectopic expression decreases tumorigenesis of cells protects mice from colitis-associated development. Further, METTL14/ALKBH5/IGF2BPs combine modulate JMJD8 stability m6A-dependent manner, which increases glycolysis accelerates development by enhancing enzymatic activity PKM2. Moreover, mRNA-loaded folic acid-modified exosome–liposome hybrid nanoparticles were synthesized significantly inhibit preclinical models modulating ALKBH5/JMJD8/PKM2 axis inhibiting glycolysis. Overall, our research confirms function regulating status provides direct approach using mRNA nanotherapeutics

Язык: Английский

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m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Авг. 15, 2023

Abstract Glycolytic reprogramming is one of the most important features cancer and plays an integral role in progression cancer. In cells, changes glucose metabolism meet needs self-proliferation, angiogenesis lymphangiogenesis, metastasis, also affect immune escape, prognosis evaluation therapeutic effect The n6-methyladenosine (m6A) modification RNA widespread eukaryotic cells. Dynamic reversible m6A modifications are widely involved regulation stem cell renewal differentiation, tumor therapy resistance, microenvironment, metabolism. Lately, more evidences show that can glycolysis process tumors a variety ways to regulate biological behavior tumors. this review, we discussed genesis development, elaborated detail profound impact on different by regulating glycolysis. We believe modified has great significance potential for treatment.

Язык: Английский

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

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 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.

Язык: Английский

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Neutrophil extracellular traps promote growth of lung adenocarcinoma by mediating the stability of m6A‐mediated SLC2A3 mRNA‐induced ferroptosis resistance and CD8(+) T cell inhibition

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(2)

Опубликована: Янв. 26, 2025

Abstract To investigate the potential mechanisms underlying neutrophil extracellular traps (NETs) confer ferroptosis resistance and CD8(+) T cell inhibition in lung adenocarcinoma (LUAD). By intravenous injection of LLC cells into tail vein, a LUAD mouse model was created. Phorbol‐12‐myristate‐13‐acetate (PMA) stimulated neutrophils to facilitate NETs formation combined with inhibitor DNase I explore mechanism on proliferation, migration, resistance, activity. CitH3, myeloperoxidase (MPO), cell‐free DNA, MPO‐DNA levels were increased, indicating an increase LUAD. PMA promoted tumours mice, increased number CD3(+)CD4(+) cells, decreased perforin, granzyme A, B, IFNγ, TNF‐α levels, growth tumour nodules, that formation, reduced activity CD8(+)T growth. partially reversed effects PMA. proliferation while effects. Erastin inhibited migration ferroptosis. Further results showed by promoting YTHDF2‐mediated SLC2A3 mRNA degradation. Sh‐YTHDF2 effect whereas si‐SLC2A3 sh‐YTHDF2 cells. In addition, inhibiting tumours, Our suggested through

Язык: Английский

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

Materials Today Bio, Год журнала: 2022, Номер 17, С. 100503 - 100503

Опубликована: Ноя. 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.

Язык: Английский

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Research progress of N1-methyladenosine RNA modification in cancer

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 30, 2024

Abstract N1-methyladenosine (m1A) is a post-transcriptionally modified RNA molecule that plays pivotal role in the regulation of various biological functions and activities. Especially cancer cell invasion, proliferation cycle regulation. Over recent years, there has been burgeoning interest investigating m1A modification RNA. Most studies have focused on enrichment areas different regions. This review provides comprehensive overview methodologies employed for detection modification. Furthermore, this delves into key players modification, known as “writers,” “erasers,” “readers.” by methyltransferases, or writers, such TRMT6, TRMT61A, TRMT61B, TRMT10C, NML, and, removed demethylases, erasers, including FTO ALKBH1, ALKBH3. It recognized m1A-binding proteins YTHDF1, TYHDF2, TYHDF3, TYHDC1, also “readers”. Additionally, we explore intricate relationship between its regulators their implications development progression specific types cancer, discuss how can potentially facilitate discovery novel approaches diagnosis, treatment, prognosis. Our summary methylated adenosine methods regulatory mechanisms cancers useful insights

Язык: Английский

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