An Ruijie, Shao Yingjie, Gu Wendong
Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, China.
J Transl Med. 2025 Aug 13;23(1):905. doi: 10.1186/s12967-025-06938-w.
m6A RNA methylation represents the most prevalent epitranscriptomic modification and modulates diverse dimensions of RNA metabolism. As a dynamic and reversible post-transcriptional mark, m6A is broadly distributed across multiple RNA types, including mRNA, ribosomal RNA (rRNA), microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and small nuclear RNA (snRNA). ALKB homolog 5 (ALKBH5), an m6A demethylase, has been extensively characterized for its involvement in tumorigenesis and progression through the removal of methylated modification from RNA, subsequently influencing RNA metabolism and gene expression regulation. A growing body of evidence indicates that ALKBH5 contributes to the therapeutic response in various cancers. Its aberrant expression is frequently observed across malignancies, where it modulates oncoprotein levels, promotes tumor initiation, and accelerates cancer cell proliferation, progression, and metastasis. Nevertheless, its implications for therapy responsiveness and the emergence of drug resistance remain poorly understood. This review centers on ALKBH5-mediated regulatory pathways and mechanisms in the contexts of chemotherapy, radiotherapy, and immunotherapy in malignancies, while also evaluating the therapeutic relevance of ALKBH5 as a molecular target and the potential of its pharmacological inhibitors.
m6A RNA甲基化是最普遍的表观转录组修饰，可调节RNA代谢的多个方面。作为一种动态可逆的转录后标记，m6A广泛分布于多种RNA类型中，包括信使核糖核酸（mRNA）、核糖体RNA（rRNA）、微小核糖核酸（miRNA）、长链非编码RNA（lncRNA）、环状RNA（circRNA）和小核RNA（snRNA）。ALKB同源物5（ALKBH5）是一种m6A去甲基化酶，通过去除RNA上的甲基化修饰，参与肿瘤发生和进展，进而影响RNA代谢和基因表达调控，这一过程已得到广泛研究。越来越多的证据表明，ALKBH5在多种癌症的治疗反应中发挥作用。在各种恶性肿瘤中经常观察到其异常表达，它可调节癌蛋白水平、促进肿瘤起始并加速癌细胞增殖、进展和转移。然而，其对治疗反应性和耐药性产生的影响仍知之甚少。本综述聚焦于ALKBH5在恶性肿瘤化疗、放疗和免疫治疗背景下介导的调控途径和机制，同时评估ALKBH5作为分子靶点的治疗相关性及其药理抑制剂的潜力。
