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RNA N6-methyladenosine modification in solid tumors: new therapeutic frontiers

Cancer Gene Therapy volume 27, pages 625–633 (2020)Cite this article

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Abstract

Epigenetic mRNA modification is an evolving field. N6-methyladenosine (m6A) is the most frequent internal transcriptional modification in eukaryotic messenger RNAs (mRNAs). This review will discuss the functions of the m6A mRNA machinery, including its “writers” that are components of the methyltransferase complex, its “readers” and its “erasers” (specifically FTO and ALKBH5) in cancer. The writers deposit the m6A and include METTL3, METTL14, WTAP, VIRMA, and RBM15. M6A methylation is removed by the m6A demethylases (FTO and ALKBH5). Lastly, the most diverse members are the readers that can contribute to mRNA splicing, stability, translation, and nuclear export. Many of these functions continue to be elucidated. The dysregulation of this machinery in various malignancies and the associated impact on tumorigenesis and drug response will be discussed herein with a focus on solid tumors. It is clear that, by contributing to either mRNA stability or translation, there are downstream targets that are impacted, contributing to cancer progression and the self-renewal ability of cancer stem cells.

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Fig. 1: m6A modification machinery summary.

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Acknowledgements

We apologize to colleagues whose work could not be included owing to space limitations.

Funding

This work was supported in part by the National Institute of Health (NIH) Grants R01 CA214965 (to JC), R01 CA236399 (to JC), R01 CA211614 (to JC), R56 DK120282 (to JC), as well as the Norman and Sadie Lee Grant City of Hope (to LM) and PanCan Translational Grant 2019 (to LM). JC is a Leukemia & Lymphoma Society (LLS) Scholar.

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  1. Department of Surgery and Immuno-Oncology, City of Hope, Duarte, CA, 91010, USA

    Laleh Melstrom

  2. Department of Systems Biology and The Gehr Family Center for Leukemia Research, The Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA

    Jianjun Chen

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Correspondence to Laleh Melstrom.

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JC has a patent filed based on his R-2HG/FTO work. JC is a scientific founder and the chief scientific officer of Genovel Biotech Corp. and also holds equity with this company.

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Melstrom, L., Chen, J. RNA N6-methyladenosine modification in solid tumors: new therapeutic frontiers. Cancer Gene Ther 27, 625–633 (2020). https://doi.org/10.1038/s41417-020-0160-4

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