Xiao Dongqiong, Su Xiaojuan
Department of Emergency, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University, Chengdu, China.
Front Pharmacol. 2025 Apr 17;16:1534655. doi: 10.3389/fphar.2025.1534655. eCollection 2025.
Patients diagnosed with clear cell renal carcinoma (ccRCC) frequently exhibit metastatic disease, which complicates treatment strategies, underscoring the urgent need for mechanistic insights and early diagnostic biomarkers. Current research is dedicated to uncovering the mechanisms behind ccRCC development and resistance to treatment, with a particular focus on the role of methyltransferase-like 3 (METTL3) in RNA N-methyladenosine modification, a key gene regulatory process. This review synthesizes current evidence on METTL3's functions, revealing its oncogenic activity through mA-mediated regulation of RNA stability and translation, which promotes tumor progression, metastasis, and chemoresistance. We further explore METTL3's dual diagnostic and therapeutic relevance, including its utility as a prognostic biomarker and its targeting via novel strategies such as small-molecule inhibitors (e.g., ) and combination therapies with mTOR or immune checkpoint inhibitors. By consolidating these advances, this review positions METTL3 as a critical node for advancing precision medicine in ccRCC.
被诊断为肾透明细胞癌（ccRCC）的患者经常出现转移性疾病，这使治疗策略变得复杂，凸显了对发病机制和早期诊断生物标志物的迫切需求。目前的研究致力于揭示ccRCC发生和治疗耐药背后的机制，特别关注甲基转移酶样3（METTL3）在RNA N-甲基腺苷修饰（一种关键的基因调控过程）中的作用。本综述综合了目前关于METTL3功能的证据，揭示了其通过mA介导的RNA稳定性和翻译调控发挥致癌活性，促进肿瘤进展、转移和化疗耐药。我们进一步探讨了METTL3在诊断和治疗方面的双重相关性，包括其作为预后生物标志物的效用，以及通过小分子抑制剂（如）和与mTOR或免疫检查点抑制剂联合治疗等新策略对其进行靶向治疗。通过整合这些进展，本综述将METTL3定位为推进ccRCC精准医学的关键节点。
