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The role of NSD1, NSD2, and NSD3 histone methyltransferases in solid tumors

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Abstract

NSD1, NSD2, and NSD3 constitute the nuclear receptor-binding SET Domain (NSD) family of histone 3 lysine 36 (H3K36) methyltransferases. These structurally similar enzymes mono- and di-methylate H3K36, which contribute to the maintenance of chromatin integrity and regulate the expression of genes that control cell division, apoptosis, DNA repair, and epithelial–mesenchymal transition (EMT). Aberrant expression or mutation of members of the NSD family is associated with developmental defects and the occurrence of some types of cancer. In this review, we discuss the effect of alterations in NSDs on cancer patient’s prognosis and response to treatment. We summarize the current understanding of the biological functions of NSD proteins, focusing on their activities and the role in the formation and progression in solid tumors biology, as well as how it depends on tumor etiologies. This review also discusses ongoing efforts to develop NSD inhibitors as a promising new class of cancer therapeutic agents.

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Acknowledgements

Figures 1, 3, and 4 were created with BioRender.com.

Funding

NIH R01 CA218802 grant, and the NCI NIH Core Grant P30 CA060553 to the Robert H Lurie Comprehensive Cancer Center at Northwestern University, Translational Bridge Award from Northwestern University (to Y.B.). This study was also partially supported by 1P50 DE030707-01 and USAMRAA W81XWH2110487 (to E.G.), NIH/NCI R01CA227918 (to J.Y.) Department of Defense grants W81XWH-17-1-0405 and W81XWH-17-1-0578 (to J.Y.), R01DE027809 to E. I., and Prostate Cancer Foundation 2017CHAL2008 (to J.Y.); J.K., and E.G. were in part supported by the NCI Core Grant P30 CA006927 (to Fox Chase Cancer Center).

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 303 E. Superior Street, Chicago, IL, 60611, USA

    Iuliia Topchu, Rajendra P. Pangeni, Igor Bychkov & Yanis Boumber

  2. Department of Natural and Applied Sciences, Nexus Institute of Research and Innovation (NIRI), Sitapakha, Mahalaxmi-4, Lalitpur, Bagmati, 44700, Nepal

    Rajendra P. Pangeni

  3. Molecular Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    Sven A. Miller, Erica Golemis & John Karanicolas

  4. Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, 60637, USA

    Evgeny Izumchenko

  5. Department of Medicine-Hematology/Oncology and Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, 303 E. Superior Street, Chicago, IL, 60611, USA

    Jindan Yu

  6. Department of Cancer and Cellular Biology, Lewis Katz School of Medicine at Temple University, 3500 North Broad St, Philadelphia, PA, 19140, USA

    Erica Golemis

  7. Moulder Center for Drug Discovery Research, Temple University School of Pharmacy, Philadelphia, PA, 19140, USA

    John Karanicolas

  8. Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, ul. 74 Karl Marks, Kazan, 420012, Russia

    Yanis Boumber

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  1. Iuliia Topchu
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Contributions

IT, RP and IB conducted the literature review and wrote the first draft. IT, RP and SM prepared the figures and tables. JK, JY, EI, EG, and YB conducted reviewing proofreading and content processing.

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Correspondence to Yanis Boumber.

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Topchu, I., Pangeni, R.P., Bychkov, I. et al. The role of NSD1, NSD2, and NSD3 histone methyltransferases in solid tumors. Cell. Mol. Life Sci. 79, 285 (2022). https://doi.org/10.1007/s00018-022-04321-2

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