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PRMT5: a putative oncogene and therapeutic target in prostate cancer

Cancer Gene Therapy volume 29, pages 264–276 (2022)Cite this article

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Abstract

Protein arginine methyltransferase 5 (PRMT5) was discovered two decades ago. The first decade focused on the biochemical characterization of PRMT5 as a regulator of many cellular processes in a healthy organism. However, over the past decade, evidence has accumulated to suggest that PRMT5 may function as an oncogene in multiple cancers via both epigenetic and non-epigenetic mechanisms. In this review, we focus on recent progress made in prostate cancer, including the role of PRMT5 in the androgen receptor (AR) expression and signaling and DNA damage response, particularly DNA double-strand break repair. We also discuss how PRMT5-interacting proteins that are considered PRMT5 cofactors may cooperate with PRMT5 to regulate PRMT5 activity and target gene expression, and how PRMT5 can interact with other epigenetic regulators implicated in prostate cancer development and progression. Finally, we suggest that targeting PRMT5 may be employed to develop multiple therapeutic approaches to enhance the treatment of prostate cancer.

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Fig. 1: Mechanisms of PRMT5-driven regulation of AR signaling in prostate cancer.
Fig. 2: Role of PRMT5 in DNA damage response in prostate cancer.
Fig. 3: Potential interplay of PRMT5 with other epigenetic regulators.

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Acknowledgements

This work was supported by following grants: U.S. Army Medical Research Acquisition Activity, Prostate Cancer Research Program (PC11190, PC120512, PC150697), NCI R01CA212403 and P30CA082709, Purdue University Center for Cancer Research Small Grants, and Purdue Research Foundation Research Grant. J. L. Owens was supported by the Indiana Clinical and Translational Sciences Institute (CTSI) Pre-Doctoral Fellowship, which was made possible with partial support from Grant Numbers TL1 TR001107, TL1 TR002531, UL1 TR001108, and UL1 TR002529 (A. Shekhar, PI) from the NIH, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. A. M. Asberry was supported by NIH T32 Grant NIH T32GM125620.

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Authors and Affiliations

  1. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA

    Elena Beketova, Jake L. Owens, Andrew M. Asberry & Chang-Deng Hu

  2. Purdue University Interdisciplinary Life Sciences Graduate Program, Purdue University, West Lafayette, IN, USA

    Elena Beketova & Andrew M. Asberry

  3. Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, USA

    Chang-Deng Hu

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  1. Elena Beketova
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  2. Jake L. Owens
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Correspondence to Chang-Deng Hu.

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Beketova, E., Owens, J.L., Asberry, A.M. et al. PRMT5: a putative oncogene and therapeutic target in prostate cancer. Cancer Gene Ther 29, 264–276 (2022). https://doi.org/10.1038/s41417-021-00327-3

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  • DOI: https://doi.org/10.1038/s41417-021-00327-3

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