{"title":"揭示mettl3介导的m6A RNA修饰在膀胱癌中的双重作用：机制、治疗脆弱性和临床意义。","authors":"Hua Chun, Kangzhuo Baima","doi":"10.1080/15384047.2025.2545057","DOIUrl":null,"url":null,"abstract":"<p><p>Bladder cancer (BC) remains challenging due to its recurrence and metastasis, with METTL3-mediated m<sup>6</sup> A RNA modification emerging as a key oncogenic driver. This review synthesizes METTL3's roles in BC progression, including tumor initiation, metastasis, stemness, and therapy resistance. We detail its regulation of critical pathways (e.g. HIF1A/IGF2BP3/BIRC5, AFF4/NF-κB/c-MYC) and dual functions in RNA stability and epigenetic crosstalk with DNA methylation. METTL3 promotes chemoresistance (e.g. circ0008399/WTAP/TNFAIP3) and immune evasion (PD-L1 stabilization), while its overexpression correlates with poor prognosis and cisplatin resistance. By integrating METTL3's interactions with m<sup>6</sup> A readers (YTHDF1/2, IGF2BP3) and erasers (ALKBH5), we propose targeting METTL3 as a strategy to enhance chemotherapy and immunotherapy efficacy. This work underscores METTL3's potential as a diagnostic biomarker and therapeutic target, advancing precision oncology in BC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2545057"},"PeriodicalIF":4.6000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unraveling the dual role of METTL3-mediated m<sup>6</sup>A RNA modification in bladder cancer: mechanisms, therapeutic vulnerabilities, and clinical implications.\",\"authors\":\"Hua Chun, Kangzhuo Baima\",\"doi\":\"10.1080/15384047.2025.2545057\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Bladder cancer (BC) remains challenging due to its recurrence and metastasis, with METTL3-mediated m<sup>6</sup> A RNA modification emerging as a key oncogenic driver. This review synthesizes METTL3's roles in BC progression, including tumor initiation, metastasis, stemness, and therapy resistance. We detail its regulation of critical pathways (e.g. HIF1A/IGF2BP3/BIRC5, AFF4/NF-κB/c-MYC) and dual functions in RNA stability and epigenetic crosstalk with DNA methylation. METTL3 promotes chemoresistance (e.g. circ0008399/WTAP/TNFAIP3) and immune evasion (PD-L1 stabilization), while its overexpression correlates with poor prognosis and cisplatin resistance. By integrating METTL3's interactions with m<sup>6</sup> A readers (YTHDF1/2, IGF2BP3) and erasers (ALKBH5), we propose targeting METTL3 as a strategy to enhance chemotherapy and immunotherapy efficacy. This work underscores METTL3's potential as a diagnostic biomarker and therapeutic target, advancing precision oncology in BC.</p>\",\"PeriodicalId\":9536,\"journal\":{\"name\":\"Cancer Biology & Therapy\",\"volume\":\"26 1\",\"pages\":\"2545057\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Biology & Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/15384047.2025.2545057\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biology & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15384047.2025.2545057","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/8 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
膀胱癌（BC）由于其复发和转移仍然具有挑战性，mettl3介导的m6 A RNA修饰成为关键的致癌驱动因素。本文综述了METTL3在BC进展中的作用，包括肿瘤起始、转移、干性和治疗抵抗。我们详细介绍了它对关键通路（例如HIF1A/IGF2BP3/BIRC5， AFF4/NF-κB/c-MYC）的调控以及RNA稳定性和表观遗传串扰与DNA甲基化的双重功能。METTL3促进化疗耐药（如circ0008399/WTAP/TNFAIP3）和免疫逃避（PD-L1稳定），而其过表达与预后不良和顺铂耐药相关。通过整合METTL3与m6 A解读子（YTHDF1/2、IGF2BP3）和擦除子（ALKBH5）的相互作用，我们提出靶向METTL3作为提高化疗和免疫治疗疗效的策略。这项工作强调了METTL3作为诊断生物标志物和治疗靶点的潜力，促进了BC的精准肿瘤学。
Unraveling the dual role of METTL3-mediated m6A RNA modification in bladder cancer: mechanisms, therapeutic vulnerabilities, and clinical implications.
Bladder cancer (BC) remains challenging due to its recurrence and metastasis, with METTL3-mediated m6 A RNA modification emerging as a key oncogenic driver. This review synthesizes METTL3's roles in BC progression, including tumor initiation, metastasis, stemness, and therapy resistance. We detail its regulation of critical pathways (e.g. HIF1A/IGF2BP3/BIRC5, AFF4/NF-κB/c-MYC) and dual functions in RNA stability and epigenetic crosstalk with DNA methylation. METTL3 promotes chemoresistance (e.g. circ0008399/WTAP/TNFAIP3) and immune evasion (PD-L1 stabilization), while its overexpression correlates with poor prognosis and cisplatin resistance. By integrating METTL3's interactions with m6 A readers (YTHDF1/2, IGF2BP3) and erasers (ALKBH5), we propose targeting METTL3 as a strategy to enhance chemotherapy and immunotherapy efficacy. This work underscores METTL3's potential as a diagnostic biomarker and therapeutic target, advancing precision oncology in BC.
期刊介绍：
Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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