REVIEW: The Role of m⁶A-RNA Methylation in the Development, Progression, and Treatment Response of Bladder Cancer

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Tatiana Sinyagovskaya^1,a*, Yuliya Li², Natalya Vinchevskaya-Khmelnitskaya², Aisha Agabalaeva², Natalia Ponomareva¹, Sergey Brezgin¹, Irina Goptar¹, Vladimir Chulanov^3,4, Alim Dymov², Andrey Vinarov², Dmitry Kostyushev^1,4,5, and Anastasiya Kostyusheva¹

¹Laboratory of Genetic Technologies, Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia

²Institute for Urology and Reproductive Health, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia

³Department of Infectious Diseases, Diseases, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia

⁴Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

⁵Faculty of Bioengineering and Bioinformatics, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received: December 11, 2024; Revised: April 20, 2025; Accepted: April 23, 2025

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Bladder cancer (BCa) remains a significant clinical challenge because of high recurrence rates and variable response to immunotherapy and chemotherapy. Recent studies have highlighted the role of N6-methyladenosine (m⁶A) modification in RNA in the regulation of various cellular processes, including tumor progression and drug resistance. The review examines the impact of m⁶A methylation on BCa pathogenesis, with a particular special focus on the role of m⁶A pathway factors and m⁶A-modified RNAs in tumorigenesis, proliferation, invasion, and migration of cancer cells. The mechanisms of m⁶A-mediated chemotherapy resistance in BCa cells are discussed, including single nucleotide polymorphisms in m⁶A-associated patterns. Significant advances in the high-throughput analysis of m⁶A methylation have enabled development of novel m⁶A-based biomarkers for the risk assessment, early diagnostics, and prediction of relapse and treatment response in BCa. The review outlines the prospects of the m⁶A-based molecular diagnostics in BCa.

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KEY WORDS: m⁶A, N6-methyladenosine, bladder cancer (BCa), biomarker, prognosis

DOI: 10.1134/S0006297924604441

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