Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(3)

Опубликована: Март 1, 2024

Abstract Heightened lactate production in cancer cells has been linked to various cellular mechanisms such as angiogenesis, hypoxia, macrophage polarisation and T‐cell dysfunction. The lactate‐induced lactylation of histone lysine residues is noteworthy, it functions an epigenetic modification that directly augments gene transcription from chromatin. This originating effectively fosters a reliance on transcription, thereby expediting tumour progression development. Herein, this review explores the correlation between characteristics, revealing innovative process enhances vulnerability malignancy. Moreover, imperative acknowledge paramount importance acknowledging therapeutic methodologies for proficiently managing by precisely targeting signalling. comprehensive illuminates crucial yet inadequately investigated aspect lactylation, providing valuable insights into its clinical ramifications prospective interventions centred lactylation.

Язык: Английский

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Quercetin‐Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects

Advanced Science, Год журнала: 2024, Номер 11(29)

Опубликована: Май 15, 2024

Abstract Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, is closely related to the occurrence progression of various systemic diseases. However, elucidating processes periodontal promoting bone regeneration remains a challenge. Here, quercetin demonstrated reduce oxidative stress state orofacial mesenchymal stem cells (OMSCs) in vitro affect osteogenic growth OMSCs through molecular mechanisms that mediate m6A change Per1. Nevertheless, limited therapeutic efficacy medication limitations local resulting from small, moist, highly dynamic environment make it challenging treat tissues with medication. Herein, biosafe injectable hydrogel drug‐controlled delivery system constructed as bone‐enhancing factory loaded injury tissues. This drug‐carrying made up nanoscale bioglass microspheres light‐cured hydrogel, allows effective drug particle loading cementation moist environment. Furthermore, demonstrates ability stimulate differentiation Per1‐dependent manner, which ultimately promotes repair, suggesting this has potential for clinical therapy.

Язык: Английский

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Oncometabolite D-2HG drives tumor metastasis and protumoral macrophage polarization by targeting FTO/m6A/ANGPTL4/integrin axis in triple-negative breast cancer

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Фев. 6, 2025

Abstract Background D-2-hydroxyglutarate (D-2HG), an oncometabolite derived from the tricarboxylic acid cycle. Previous studies have reported diverse effects of D-2HG in pathophysiological processes, yet its role breast cancer remains largely unexplored. Methods We applied advanced biosensor approach to detect levels samples. then investigated biological functions through multiple vitro and vivo assays. A joint MeRIP-seq RNA-seq strategy was used identify target genes regulated by D-2HG-mediated N6-methyladenosine (m 6 A) modification. RNA pull-down assays were further reader that could specifically recognize m modification on angiopoietin like 4 (ANGPTL4) mRNA immunoprecipitation confirm findings. Results found accumulated triple-negative (TNBC), exerting oncogenic both promoting TNBC cell growth metastasis. Mechanistically, enhanced global modifications cells, notably upregulating ANGPTL4 mRNA, which mediated inhibition Fat-mass obesity-associated protein (FTO), resulting increased recognition A-modified YTH binding F1 (YTHDF1), thereby translation ANGPTL4. As a secretory protein, subsequently activated integrin-mediated JAK2/STAT3 signaling cascade cells autocrine signaling. Notably, knockdown or treatment with GLPG1087 (an integrin antagonist) significantly reduced D-2HG-induced proliferation metastasis cells. Additionally, promote macrophage M2 polarization within tumor microenvironment via paracrine signaling, driving progression. The association poor prognosis patients underscores clinical relevance. Conclusions Our study unveils previously unrecognized for progression targeting D-2HG/FTO/m A/ANGPTL4/integrin axis can serve as promising therapeutic patients.

Язык: Английский

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Epigenetic control of skeletal muscle atrophy

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Июль 8, 2024

Abstract Skeletal muscular atrophy is a complex disease involving large number of gene expression regulatory networks and various biological processes. Despite extensive research on this topic, its underlying mechanisms remain elusive, effective therapeutic approaches are yet to be established. Recent studies have shown that epigenetics play an important role in regulating skeletal muscle atrophy, influencing the numerous genes associated with condition through addition or removal certain chemical modifications at molecular level. This review article comprehensively summarizes different types DNA, histones, RNA, their known regulators. We also discuss how epigenetic change during process by which proteins control assess translational potential. The stem cells highlighted. In addition, we propose alternative splicing interacts regulate mass, offering novel perspective enhances our understanding inheritance’s network governing atrophy. Collectively, advancements provide invaluable insights into study Moreover, knowledge paves way for identifying new avenues development more strategies pharmaceutical interventions.

Язык: Английский

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Triple‑negative breast cancer cell‑derived piR‑31115 promotes the proliferation and migration of endothelial cells via METTL3‑mediated m6A modification of YAP1

Oncology Reports, Год журнала: 2025, Номер 53(3)

Опубликована: Янв. 16, 2025

Язык: Английский

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RNA Methylation Homeostasis in Ocular Diseases: All Eyes on Me

Progress in Retinal and Eye Research, Год журнала: 2025, Номер unknown, С. 101335 - 101335

Опубликована: Янв. 1, 2025

Язык: Английский

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Single-molecule m6A detection empowered by endogenous labeling unveils complexities across RNA isoforms

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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RNA Modification in Metabolism

MedComm, Год журнала: 2025, Номер 6(3)

Опубликована: Март 1, 2025

ABSTRACT Epigenetic regulation in disease development has been witnessed within this decade. RNA methylation is the predominant form of epigenetic regulation, and most prevalent modification N6‐methyladenosine (m 6 A). Recently, emerged as a potential target for treatment. posttranscriptional gene expression that involved both physiological pathological processes. Evidence suggests m A significantly affects metabolism, its abnormal changes have observed variety diseases. Metabolic diseases are series caused by metabolic processes body, common include diabetes mellitus, obesity, nonalcoholic fatty liver disease, etc.; although pathogenesis these differs from each other to current understanding, recent studies suggested pivotal role modulating diseases, A‐based drug on agenda. This paper reviewed understanding hoping provide systematic information those area.

Язык: Английский

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RNA N4‐acetylcytidine modification and its role in health and diseases

MedComm, Год журнала: 2025, Номер 6(1)

Опубликована: Янв. 1, 2025

Abstract N4‐acetylcytidine (ac4C) modification is a crucial RNA widely present in eukaryotic RNA. Previous studies have demonstrated that ac4C plays pivotal role viral infections. Despite numerous highlighting the strong correlation between and cancer progression, its detailed roles molecular mechanisms normal physiological processes progression remain incompletely understood. This review first outlines key regulatory enzyme mediating modification, N‐acetyltransferase 10 (NAT10), including critical regulating stability, transcriptional efficiency, translational fidelity. Additionally, it systematically summarizes essential functions of biological processes, stem cell fate determination, spermatogenesis oogenesis, embryonic development, cellular senescence, bone remodeling. Furthermore, this delves into central malignant proliferation, cycle arrest, EMT, drug resistance, death, metabolism, tumor immunotherapy. It also emphasizes potential NAT10 as prognostic biomarker therapeutic target for disease treatment. In summary, clarifies multifaceted both health explores NAT10‐targeted therapies with aim advancing research improving patient outcomes.

Язык: Английский

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M6A Demethylase ALKBH5 in Human Diseases: From Structure to Mechanisms

Biomolecules, Год журнала: 2025, Номер 15(2), С. 157 - 157

Опубликована: Янв. 21, 2025

N6-methyladenosine (m6A) is the most abundant, dynamically reversible, and evolutionarily conserved internal chemical modification in eukaryotic RNA. It emerging as critical for regulating gene expression at post-transcriptional level by affecting RNA metabolism through, example, pre-mRNA processing, mRNA decay, translation. ALKBH5 has recently been identified an endogenous m6A demethylase implicated a multitude of biological processes. This review provides overview structural functional characteristics involvement diverse human diseases, including metabolic, immune, reproductive, nervous system disorders, well development inhibitors. In summation, this highlights current understanding structure, functions, detailed mechanisms various physiological pathological processes valuable insights clinical applications foundational research within related fields.

Язык: Английский

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