Role of m6A writers, erasers and readers in cancer

Experimental Hematology and Oncology, Год журнала: 2022, Номер 11(1)

Опубликована: Авг. 9, 2022

Abstract The N(6)-methyladenosine (m6A) modification is the most pervasive of human RNAs. In recent years, an increasing number studies have suggested that m6A likely plays important roles in cancers. Many demonstrated involved biological functions cancer cells, such as proliferation, invasion, metastasis, and drug resistance. addition, closely related to prognosis patients. this review, we highlight advances understanding function various We emphasize importance progression look forward describe future research directions.

Язык: Английский

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FTO suppresses glycolysis and growth of papillary thyroid cancer via decreasing stability of APOE mRNA in an N6-methyladenosine-dependent manner

Journal of Experimental & Clinical Cancer Research, Год журнала: 2022, Номер 41(1)

Опубликована: Янв. 28, 2022

N6-methyladenosine (m6A) modification is the most common chemical in mammalian mRNAs, and it plays important roles by regulating several cellular processes. Previous studies report that m6A implicated modulating tumorigenesis progression. However, dysregulation of effect demethylase fat-mass obesity-associated protein (FTO) on glucose metabolism has not been fully elucidated papillary thyroid cancer (PTC).Quantitative real-time PCR (qRT-PCR), western blotting immunohistochemistry were performed to explore expression profile FTO PTC tissues adjacent non-cancerous tissues. Effects glycolysis growth investigated through vitro vivo experiments. Mechanism FTO-mediated was explored transcriptome-sequencing (RNA-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP-qPCR, luciferase reporter assays, stability assay assay.FTO significantly downregulated Functional analysis showed inhibited growth. Further analyses conducted cells Apolipoprotein E (APOE) identified as target gene for using RNA-seq MeRIP-seq. knockdown increased APOE mRNA upregulated its expression. recognized stabilized reader IGF2BP2. The findings also promoted tumor PTC. Analysis FTO/APOE axis inhibits IL-6/JAK2/STAT3 signaling pathway.FTO acts a suppressor inhibit current study IGF2BP2-mediated may glycolytic pathway, thus abrogating

Язык: Английский

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Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets

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

Опубликована: Июнь 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Язык: Английский

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Metabolic Reprogramming Driven by IGF2BP3 Promotes Acquired Resistance to EGFR Inhibitors in Non–Small Cell Lung Cancer

Cancer Research, Год журнала: 2023, Номер 83(13), С. 2187 - 2207

Опубликована: Апрель 16, 2023

Abstract Acquired resistance represents a bottleneck for effective molecular targeted therapy in lung cancer. Metabolic adaptation is distinct hallmark of human cancer that might contribute to acquired resistance. In this study, we discovered novel mechanism EGFR tyrosine kinase inhibitors (TKI) mediated by IGF2BP3-dependent cross-talk between epigenetic modifications and metabolic reprogramming through the IGF2BP3–COX6B2 axis. IGF2BP3 was upregulated patients with TKI-resistant non–small cell cancer, high expression correlated reduced overall survival. Upregulated RNA binding protein cells sensitivity TKI treatment exacerbated development drug via promoting oxidative phosphorylation (OXPHOS). COX6B2 mRNA bound IGF2BP3, required increased OXPHOS EGFR-TKI IGF2BP3. Mechanistically, 3′-untranslated region an m6A-dependent manner increase stability. Moreover, axis regulated nicotinamide metabolism, which can alter promote Inhibition IACS-010759, small-molecule inhibitor, resulted strong growth suppression vitro vivo gefitinib-resistant patient-derived xenograft model. Collectively, these findings suggest plays critical role confers targetable vulnerability overcome EGFR-TKIs Significance: stabilizes drive provides therapeutic strategy targeting transitions.

Язык: Английский

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Critical roles and clinical perspectives of RNA methylation in cancer

MedComm, Год журнала: 2024, Номер 5(5)

Опубликована: Май 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.

Язык: Английский

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YTHDF2-mediated m6A modification of ONECUT2 promotes stemness and oxaliplatin resistance in gastric cancer through transcriptionally activating TFPI

Drug Resistance Updates, Год журнала: 2025, Номер 79, С. 101200 - 101200

Опубликована: Янв. 2, 2025

Язык: Английский

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Interplay Among Metabolism, Epigenetic Modifications, and Gene Expression in Cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Дек. 24, 2021

Epigenetic modifications and metabolism are two fundamental biological processes. During tumorigenesis cancer development both epigenetic metabolic alterations occur often intertwined together. contribute to reprogramming by modifying the transcriptional regulation of enzymes, which is crucial for glucose metabolism, lipid amino acid metabolism. Metabolites provide substrates modifications, including histone modification (methylation, acetylation, phosphorylation), DNA RNA methylation non-coding RNAs. Simultaneously, some metabolites can also serve as nonhistone post-translational that have an impact on tumors. And enzymes regulate independent their metabolites. In addition, produced gut microbiota influence host Understanding crosstalk among gene expression in may help researchers explore mechanisms carcinogenesis progression metastasis, thereby strategies prevention therapy cancer. this review, we summarize progress understanding interactions between epigenetics.

Язык: Английский

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m6A demethylase FTO renders radioresistance of nasopharyngeal carcinoma via promoting OTUB1-mediated anti-ferroptosis

Translational Oncology, Год журнала: 2022, Номер 27, С. 101576 - 101576

Опубликована: Ноя. 4, 2022

Язык: Английский

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MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

Cell Death Discovery, Год журнала: 2022, Номер 8(1)

Опубликована: Фев. 8, 2022

N6-Methyladenosine (m6A) modification is the most abundant RNA in eukaryotic cells. IGF2BP3, a well-known m6A reader, deregulated many cancers, but its role nasopharyngeal carcinoma (NPC) remains unclear. In this work, IGF2BP3 was upregulated NPC tissues and The high level of positively related to late clinical stages, node metastasis, poor outcomes. Moreover, accelerated cell tumor progression metastasis vitro vivo. Upstream mechanism analyses indicated that expression head neck tumors mainly due mRNA amplification. Luciferase assay chromatin immunoprecipitation (CHIP) depicted MYC effectively bound promoter thereby improving transcriptional activity. Results also showed not only correlated with KPNA2 modulated KPNA2. (MeRIP) stability experiments verified silencing significantly inhibited KPNA2, stabilizing Rescue proved effect inhibiting or overexpressing on cells partly reversed by Collectively, MYC-activated promoted proliferation influencing m6A-modified Our findings offer new insights may serve as molecular marker potential therapeutic target for treatment.

Язык: Английский

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Novel insight into RNA modifications in tumor immunity: Promising targets to prevent tumor immune escape

The Innovation, Год журнала: 2023, Номер 4(4), С. 100452 - 100452

Опубликована: Май 29, 2023

•RNA modification is a novel hotspot of epigenetic research, affecting wide range physiological and pathological processes.•RNA plays an important role in tumor immunity.•RNA may be potential clinical therapeutic target to prevent immune escape. An immunosuppressive state typical feature the microenvironment. Despite dramatic success checkpoint inhibitor (ICI) therapy preventing cell escape from surveillance, primary acquired resistance have limited its use. Notably, recent trials shown that drugs can significantly improve outcome ICI various cancers, indicating importance modifications regulation tumors. Recently, RNA (N6-methyladenosine [m6A], N1-methyladenosine [m1A], 5-methylcytosine [m5C], etc.), areas been play crucial roles protumor antitumor immunity. In this review, we provide comprehensive understanding how m6A, m1A, m5C function immunity by directly regulating different cells as well indirectly through mechanisms, including modulating expression checkpoints, inducing metabolic reprogramming, secretion immune-related factors. Finally, discuss current status strategies targeting escape, highlighting their potential.

Язык: Английский

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