Publication: Elucidating the role of PRMTs in prostate cancer using open access databases and a patient cohort dataset
Authors
Grypari, Ioanna Maria ; Pappa, Ioanna ; Papastergiou, Thomas ; Zolota, Vassiliki ; Bravou, Vasiliki ; Melachrinou, Maria ; Megalooikonomou, Vasileios ; Tzelepi, Vasiliki
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/ 10.14670/HH-18-513
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info:eu-repo/semantics/article
Description
Abstract
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.
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