Strasenburg Wiktoria, Borowczak Jędrzej, Piątkowska Daria, Jóźwicki Jakub, Grzanka Dariusz
Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
Clinical Department of Oncology, Prof. Franciszek Łukaszczyk Oncology Centre, Bydgoszcz, Poland.
Front Oncol. 2025 Jun 26;15:1567242. doi: 10.3389/fonc.2025.1567242. eCollection 2025.
DNA methylation is the best-known epigenetic mechanism regulating gene expression without altering the DNA sequence. Its counterpart, known as DNA demethylation, is equally important and enables the activation of previously silenced genes. DNA demethylation has attracted interest in the scientific community following the landmark discovery that Ten-Eleven Translocation (TET) proteins can convert 5-methylcytosine to 5-hydroxymethylcytosine. A growing body of research indicates that changes in TET protein levels and 5-hydroxymethylcytosine content are hallmarks of cancer. These epigenetic changes appear to play a critical role in the development of malignancies characterized by high levels of somatic mutations and genetic instability. Bladder cancer is among the most common cancers worldwide and, despite aggressive treatment, remains associated with high mortality and poor prognosis. The lack of reliable diagnostic and prognostic markers poses a significant challenge in its management, highlighting the urgent need for novel biomarkers to enable earlier diagnosis and more accurate prediction of clinical outcomes. This review examines epigenetic alterations associated with bladder cancer and their clinical implications. We focus on the impact of DNA methylation and demethylation on oncogene regulation, summarize scientific evidence supporting their role in bladder cancer development and progression, and briefly explore novel therapeutic strategies targeting those epigenetic mechanisms.
DNA甲基化是最广为人知的表观遗传机制，可在不改变DNA序列的情况下调节基因表达。其对应过程，即DNA去甲基化，同样重要，它能激活先前沉默的基因。在具有里程碑意义的发现——即十一易位（TET）蛋白可将5-甲基胞嘧啶转化为5-羟甲基胞嘧啶之后，DNA去甲基化引起了科学界的关注。越来越多的研究表明，TET蛋白水平和5-羟甲基胞嘧啶含量的变化是癌症的标志。这些表观遗传变化似乎在以高水平体细胞突变和基因不稳定为特征的恶性肿瘤发展中起关键作用。膀胱癌是全球最常见的癌症之一，尽管进行了积极治疗，但死亡率仍然很高，预后很差。缺乏可靠的诊断和预后标志物给其治疗带来了重大挑战，凸显了迫切需要新型生物标志物以实现早期诊断和更准确预测临床结果的需求。本综述探讨了与膀胱癌相关的表观遗传改变及其临床意义。我们重点关注DNA甲基化和去甲基化对癌基因调控的影响，总结支持它们在膀胱癌发生和发展中作用的科学证据，并简要探讨针对这些表观遗传机制的新型治疗策略。
