RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:METTL14 in tumor immunity: epitranscriptomic regulation and therapeutic potential.
METTL14 in tumor immunity: epitranscriptomic regulation and therapeutic potential.
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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。
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.
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