Elucidating the role of PRMTs in prostate cancer using open access databases and a patient cohort dataset
Ioanna Maria Grypari1, Ioanna Pappa2, Thomas Papastergiou2, Vasiliki Zolota1, Vasiliki Bravou3, Maria Melachrinou1, Vasileios Megalooikonomou2 and Vasiliki Tzelepi1
1Department of Pathology, School of Medicine, University of Patras, Patras, 2Multidimensional Data Analysis and Knowledge Management Laboratory, Computer Engineering and Informatics Department, School of Engineering, University of Patras, Patras and 3Department of Anatomy, Histology and Embryology, School of Medicine, University of Patras, Patras, Greece
Corresponding Author: Vasiliki Tzelepi, Department of Pathology, School of Medicine, University of Patras, Patras, Greece. e-mail: btzelepi@upatras.gr
Summary. Protein arginine methylation is an understudied epigenetic mechanism catalyzed by enzymes known as Protein Methyltransferases of Arginine (PRMTs), while the opposite reaction is performed by Jumonji domain- containing protein 6 (JMJD6). There is increasing evidence that PRMTs are deregulated in prostate cancer (PCa). In this study, the expression of two PRMT members, PRMT2 and PRMT7 as well as JMJD6, a demethylase, was analyzed in PCa. Initially, we retrieved data from The Cancer Genome Atlas (TCGA) project and the Gene Expression Omnibus (GEO) database to explore the differential expression of various PRMT family members in patients with PCa and then applied immunohistochemistry in a patient cohort across the spectrum of PCa, including non-neoplastic prostate tissue and lymph node metastatic foci. The results from the TCGA analysis revealed that PRMT7, PRMT6 and PRMT3 expression increased while PRMT2, PRMT9 and JMJD6 levels decreased in the tumor compared to non-neoplastic prostate. Results from the GEO datasets were similar, albeit not identical with the TCGA results, with PRMT7 and PRMT3 being upregulated and PRMT2 and JMJD6 being downregulated in the tumor compared to non-neoplastic tissue in some of them. In addition, PRMT7 levels decreased with stage and grade progression in the TCGA analysis. In the patient cohort, both PRMTs and JMJD6 were overexpressed in PCa compared to non-neoplastic tissue, and nuclear PRMT2 and JMJD6 were upregulated in lymph node metastasis, too. PRMT7 and JMJD6 expression were upregulated with the progression of stage and JMJD6 was also increased with the elevation of grade. After androgen ablation therapy, nuclear expression of PRMT7 and JMJD6 were elevated compared to untreated tumors. PRMT2, PRMT7 and JMD6 were also correlated with markers of EMT and cell cycle regulators. Finally, our findings indicate that PRMTs and JMJD6 are involved in prostate cancer progression and revealed a potential interplay of PRMTs with EMT mediators, underscoring the need for therapeutic targeting of arginine methylation in prostate cancer. Histol Histopathol 38, 287-302 (2023)
Key words: PRMTs, Prostate cancer, TCGA and GEO analysis validated with immunohistochemistry
DOI: 10.14670/HH-18-513
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ŠThe Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
