The protein arginine methyltransferases (PRMTs) PRMT1 and CARM1 as candidate epigenetic drivers in prostate cancer progression.
Journal
Medicine
ISSN: 1536-5964
Titre abrégé: Medicine (Baltimore)
Pays: United States
ID NLM: 2985248R
Informations de publication
Date de publication:
10 Sep 2021
10 Sep 2021
Historique:
received:
13
04
2021
accepted:
13
08
2021
entrez:
13
9
2021
pubmed:
14
9
2021
medline:
21
9
2021
Statut:
ppublish
Résumé
Epigenetic changes are implicated in prostate cancer (PCa) progression and resistance to therapy. Arginine residue methylation is an understudied histone post-translational modification that is increasingly associated with cancer progression and is catalyzed by enzymes called protein arginine methyltransferases (PRMTs). The molecular consequences of aberrant expression of PRMTs in PCa and the relationship between PRMTs and PCa progression are largely unknown. Using immunohistochemistry, we examined the expression of PRMT1 and CARM1, two of the best-studied PRMTs, in 288 patients across the spectrum of PCa and correlated them with markers of androgen receptor (AR) signaling, and milestones of carcinogenesis. Our findings indicate that PRMT1 and CARM1 are upregulated early in PCa progression, and that CARM1 is further upregulated after therapy. In addition, a correlation of CARM1 with AR post-translational modifications was noted in the setting of therapy resistance, highlighting CARM1 as one of the adaptation mechanisms of PCa cells in an androgen-depleted environment. Finally, CARM1 correlated with markers of cell cycle regulation, and both CARM1 and PRMT1 correlated with markers of epithelial-to-mesenchymal transition signaling. Taken together these findings indicate that an epigenetic network drives PCa progression through enhancement of milestone pathways including AR signaling, the cell cycle, and epithelial-to-mesenchymal transition.
Identifiants
pubmed: 34516499
doi: 10.1097/MD.0000000000027094
pii: 00005792-202109100-00014
pmc: PMC8428700
doi:
Substances chimiques
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
coactivator-associated arginine methyltransferase 1
EC 2.1.1.319
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e27094Subventions
Organisme : Research Committee of the University of Patras via "K. Karatheodori" program
ID : 56570000
Informations de copyright
Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to disclose.
Références
Barbieri CE, Bangma CH, Bjartell A, et al. The mutational landscape of prostate cancer. Eur Urol 2013;64:567–76.
Li L-C, Carroll PR, Dahiya R. Epigenetic changes in prostate cancer: implication for diagnosis and treatment. JNCI J Natl Cancer Inst 2005;97:103–15.
Ngollo M, Dagdemir A, Karsli-Ceppioglu S, et al. Epigenetic modifications in prostate cancer. Epigenomics 2014;6:415–26.
Tzelepi V, Logotheti S, Efstathiou E, et al. Epigenetics and prostate cancer: defining the timing of DNA methyltransferase deregulation during prostate cancer progression. Pathology 2020;52:218–27.
Zhao SG, Chen WS, Li H, et al. The DNA methylation landscape of advanced prostate cancer. Nat Genet 2020;52:778–89.
Kleb B, Estécio MRH, Zhang J, et al. Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas. Epigenetics 2016;11:184–93.
Tzelepi V, Zhang J, Lu J-FF, et al. Modeling a lethal prostate cancer variant with small-cell carcinoma features. Clin Cancer Res 2012;18:666–77.
Gal-Yam EN, Egger G, Iniguez L, et al. Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. Proc Natl Acad Sci U S A 2008;105:12979–84.
Viré E, Brenner C, Deplus R, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006;439:871–4.
Jarrold J, Davies CC. PRMTs and arginine methylation: cancer's best-kept secret? Trends Mol Med 2019;25:993–1009.
Zou S, Wang X, Liu P, Ke C, Xu S. Arginine metabolism and deprivation in cancer therapy. Biomed Pharmacother 2019;118:109210.
Li X, Wang C, Jiang H, Luo C. A patent review of arginine methyltransferase inhibitors (2010–2018). Expert Opin Ther Pat 2019;29:97–114.
Kim YR, Lee BK, Park RY, et al. Differential CARM1 expression in prostate and colorectal cancers. BMC Cancer 2010;10:01–13.
Mounir Z, Korn JM, Westerling T, et al. ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the androgen receptor. Elife 2016;5:
Hong H, Kao C, Jeng MH, et al. Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status. Cancer 2004;101:83–9.
Majumder S, Liu Y, Ford OH, Mohler JL, Whang YE. Involvement of arginine methyltransferase CARM1 in androgen receptor function and prostate cancer cell viability. Prostate 2006;66:1292–301.
Zhang J, Jing L, Li M, He L, Guo Z. Regulation of histone arginine methylation/demethylation by methylase and demethylase (review). Mol Med Rep 2019;49:3963–71.
Smith E, Zhou W, Shindiapina P, Sif S, Li C, Baiocchi RA. Recent advances in targeting protein arginine methyltransferase enzymes in cancer therapy. Expert Opin Ther Targets 2018;22:527–45.
Mathioudaki K, Papadokostopoulou A, Scorilas A, Xynopoulos D, Agnanti N, Talieri M. The PRMT1 gene expression pattern in colon cancer. Br J Cancer 2008;99:2094–9.
Zhang XP, Jiang YB, Zhong CQ, et al. PRMT1 promoted HCC growth and metastasis in vitro and in vivo via activating the STAT3 signalling pathway. Cell Physiol Biochem 2018;47:1643–54.
Mathioudaki K, Scorilas A, Ardavanis A, et al. Clinical evaluation of PRMT1 gene expression in breast cancer. Tumor Biol 2011;32:575–82.
Avasarala S, Van Scoyk M, Rathinam MKK, et al. PRMT1 is a novel regulator of epithelial-mesenchymal-transition in non-small cell lung cancer. J Biol Chem 2015;290:13479–89.
Gao G, Zhang L, Villarreal OD, et al. PRMT1 loss sensitizes cells to PRMT5 inhibition. Nucleic Acids Res 2019;47:5038–48.
Wang J, Chen L, Sinha SH, et al. Pharmacophore-based virtual screening and biological evaluation of small molecule inhibitors for protein arginine methylation. J Med Chem 2012;55:7978–87.
Chen D, Ma H, Hong H, et al. Regulation of transcription by a protein methyltransferase. Science 1999;284:2174–7.
Koryakina Y, Ta HQ, Gioeli D. Androgen receptor phosphorylation: biological context and functional consequences. Endocr Relat Cancer 2014;21:T131–45.
Kasina S, Macoska JA. The CXCL12/CXCR4 axis promotes ligand-independent activation of the androgen receptor. Mol Cell Endocrinol 2012;351:249–63.
Kim KY, Wang D-H, Campbell M, et al. PRMT4-mediated arginine methylation negatively regulates retinoblastoma tumor suppressor protein and promotes E2F-1 dissociation. Mol Cell Biol 2015;35:238–48.
Dongre A, Weinberg RA. New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 2019;20:69–84.
Gao Y, Zhao Y, Zhang J, et al. The dual function of PRMT1 in modulating epithelial-mesenchymal transition and cellular senescence in breast cancer cells through regulation of ZEB1. Sci Rep 2016;6:19874.