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  • Review Article
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RNA N6-methyladenosine modifications in urological cancers: from mechanism to application

Nature Reviews Urology (2024)Cite this article

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Abstract

The N6‐methyladenosine (m6A) modification is the most common modification of messenger RNAs in eukaryotes and has crucial roles in multiple cancers, including in urological malignancies such as renal cell carcinoma, bladder cancer and prostate cancer. The m6A RNA modification is controlled by three types of regulators, including methyltransferases (writers), demethylases (erasers) and RNA‐binding proteins (readers), which are responsible for gene regulation at the post-transcriptional level. This Review summarizes the current evidence indicating that aberrant or dysregulated m6A modification is associated with urological cancer development, progression and prognosis. The complex and context-dependent effects of dysregulated m6A modifications in urological cancers are described, along with the potential for aberrantly expressed m6A regulators to provide valuable diagnostic and prognostic biomarkers as well as new therapeutic targets.

Key points

  • RNA m6A (N6 methyladenosine) modifications contribute to the occurrence and progression of urological cancers, including renal cell carcinoma, bladder cancer and prostate cancer.

  • Aberrant m6A modification promotes malignant transformation and drives proliferation, apoptosis, migration, invasion and metastasis of urological cancers via changes in autophagy, glycolysis, mitochondrial metabolism, stemness remodelling and the tumour microenvironment.

  • RNA m6A modifications have complex and heterogeneous roles in urological cancers; some m6A regulators have both tumour-suppressing and tumour-promoting effects on cancer progression.

  • Various m6A modifiers involved in writing, reading and erasing of m6A modifications participate in intricate and dynamic signalling networks associated with urological cancer cell proliferation, differentiation, invasion and treatment resistance.

  • Preclinical studies have demonstrated potential benefits of targeting m6A modifiers in urological malignancies, but no phase II clinical trials have been conducted so far.

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Fig. 1: An overview of RNA m6A modification.
Fig. 2: M6A modifications in renal cell carcinoma.
Fig. 3: M6A modifications in bladder cancer.
Fig. 4: M6A modifications in prostate cancer.
Fig. 5: Clinical applications of m6A regulators in urological cancers.

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Acknowledgements

Q.Z.’s research is supported by funding grants from the National Natural Science Foundation of China (82273151 and 82072826).

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Authors and Affiliations

  1. Department of Urology, Peking University First Hospital, Institute of Urology, National Research Center for Genitourinary Oncology, Peking University, Beijing, China

    Lei Yang & Qian Zhang

  2. Department of Pathology, Cancer Institute and Cancer Hospital, Peking Union Medical College (PUMC), Chinese Academy of Medical Sciences, Beijing, China

    Jianming Ying

  3. Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China

    Qian Tao

  4. Department of Urology, Peking University Binhai Hospital, Tianjin, China

    Qian Zhang

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Q.Z. provided direction and guidance throughout the preparation of this Review. L.Y. wrote and edited the manuscript. J.Y. and Q.T. reviewed and edited the manuscript. All authors read and approved the final draft.

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Yang, L., Ying, J., Tao, Q. et al. RNA N6-methyladenosine modifications in urological cancers: from mechanism to application. Nat Rev Urol (2024). https://doi.org/10.1038/s41585-023-00851-x

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