N6-methyladenosine RNA modification in stomach carcinoma: Novel insights into mechanisms and implications for diagnosis and treatment

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-14 DOI:10.1016/j.bbadis.2025.167793

Zhengmao Lu , Zhaojie Lyu , Peixin Dong , Yunmei Liu , Lei Huang

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引用次数: 0

Abstract

N6-methyladenosine (m⁶A) RNA methylation is crucially involved in the genesis and advancement of gastric cancer (GC) by controlling various pathobiological aspects including gene expression, signal transduction, metabolism, cell death, epithelial-mesenchymal transition, angiogenesis, and exosome function. Despite its importance, the exact mechanisms by which m⁶A modification influences GC biology remain inadequately explored. This review consolidates the latest advances in uncovering the mechanisms and diverse roles of m⁶A in GC and proposes new research and translational directions. Key regulators (writers, readers, and erasers) of m⁶A, such as METTL3/14/16 and WTAP, significantly affect cancer progression, anticancer immune response, and treatment outcomes. m⁶A modification also impacts immune cell infiltration and the tumor microenvironment, highlighting its potential as a diagnostic and prognostic marker. Interactions between m⁶A methylation and non-coding RNAs offer further novel insights into GC development and therapeutic targets. Targeting m⁶A regulators could enhance immunotherapy response, overcome treatment resistance, and improve oncological and clinical outcomes. Models based on m⁶A can precisely predict treatment response and prognosis in GC. Additional investigation is needed to fully understand the mechanisms of m⁶A methylation and its potential clinical applications and relevance (e.g., as precise markers for early detection, prediction of outcome, and response to therapy and as therapeutic targets) in GC. Future research should focus on in vivo studies, potential clinical trials, and the examination of m⁶A modification in other types of cancers.

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N6-甲基腺苷（m6A）RNA 甲基化通过控制基因表达、信号转导、新陈代谢、细胞死亡、上皮-间质转化、血管生成和外泌体功能等各种病理生物学方面，在胃癌（GC）的发生和发展中起着至关重要的作用。尽管m6A修饰非常重要，但其影响GC生物学的确切机制仍未得到充分探索。这篇综述整合了揭示 m6A 在 GC 中的作用机制和多样性方面的最新进展，并提出了新的研究和转化方向。m6A的关键调控因子（书写者、阅读者和擦除者），如METTL3/14/16和WTAP，对癌症进展、抗癌免疫反应和治疗效果有显著影响。m6A修饰还影响免疫细胞浸润和肿瘤微环境，突出了其作为诊断和预后标志物的潜力。m6A 甲基化与非编码 RNA 之间的相互作用为 GC 的发展和治疗靶点提供了进一步的新见解。以 m6A 调节因子为靶点可以增强免疫治疗反应，克服治疗耐药性，改善肿瘤和临床预后。基于 m6A 的模型可以精确预测 GC 的治疗反应和预后。要全面了解 m6A 甲基化的机制及其在 GC 中的潜在临床应用和相关性（如作为早期检测、预后预测和治疗反应的精确标记以及作为治疗靶点），还需要进行更多的研究。未来的研究应重点关注体内研究、潜在的临床试验以及 m6A 修饰在其他类型癌症中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.