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METTL14 在肿瘤免疫中的作用:表观转录组调控及治疗潜力

英文原题:METTL14 in tumor immunity: epitranscriptomic regulation and therapeutic potential.

查看英文原题

METTL14 in tumor immunity: epitranscriptomic regulation and therapeutic potential.

PubMed 2025/10/14(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

N6-甲基腺苷(m6A)是最丰富的内部RNA修饰,由写入器、擦除器和阅读器共同调控。METTL14是m6A甲基转移酶复合物的关键组分,作为结构性支架确保底物识别和修饰精确性。除这一经典作用外,METTL14还调控多种生物学过程,包括染色质重塑、转录活性和衰老相关信号传导。近期研究强调其在肿瘤免疫中的关键功能:METTL14塑造T细胞分化、CD8+ T细胞活化以及巨噬细胞和NK细胞的活性,从而重塑肿瘤免疫微环境。此外,METTL14通过调控PD-1和PD-L1表达直接调节免疫检查点通路,将表观转录组控制与免疫逃逸和治疗耐药联系起来。METTL14表达异常与肿瘤进展和免疫逃逸相关,凸显其作为预测性生物标志物和治疗靶点的潜力。靶向METTL14,单独或与免疫检查点抑制剂联合,可能提供增强免疫治疗疗效的新策略。

展开英文摘要原文

N 6 -methyladenosine (m 6 A) is the most abundant internal RNA modification, orchestrated by writers, erasers, and readers. METTL14, a key component of the m 6 A methyltransferase complex, acts as a structural scaffold that ensures substrate recognition and modification precision.

Beyond this canonical role, METTL14 regulates multiple biological processes, including chromatin remodeling, transcriptional activity, and senescence-associated signaling. Recent studies highlight its pivotal function in tumor immunity: METTL14 shapes T cell differentiation, CD8 + T cell activation, and the activity of macrophages and NK cells, thereby remodeling the tumor immune microenvironment.

Moreover, METTL14 directly modulates immune checkpoint pathways by regulating PD-1 and PD-L1 expression, linking epitranscriptomic control with immune escape and therapeutic resistance. Aberrant METTL14 expression correlates with tumor progression and immune evasion, underscoring its potential as a predictive biomarker and therapeutic target. Targeting METTL14, alone or in combination with immune checkpoint inhibitors, may provide novel strategies to enhance immunotherapy efficacy.

论文信息

作者
Li C、Jiang X、Yuan Y、Wang Q
第一作者单位
Department of Oncology, Suining Central Hospital, Suining, Sichuan, China.China
通讯作者单位
Department of Gastrointestinal Surgical Unit, Suining Central Hospital, Suining, Sichuan, China.China
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 41164187 · DOI 10.3389/fimmu.2025.1709742