In Vivo, cilt.39, sa.2, ss.1-10, 2025 (Scopus)
Background:
Prostate cancer is a condition where cells in the prostate gland grow
uncontrollably, and it is the second leading cause of cancer-related deaths in
men. Periodontitis is considered a high-risk factor for prostate cancer, but
the genetic mechanism is unclear. This study aims to identify dysregulated
miRNAs, their associated genes, signaling pathways, and compounds linking
periodontitis to prostate cancer.
Materials and Methods:
The miRNA expression datasets of
prostate cancer and periodontitis were searched from the GEO database.
Differentially expressed miRNAs (DEmiRNAs) were identified, and common DEmiRNAs
(Co-DEmiRNAs) between both datasets were determined. The Co-DEmiRNA-target
network structure and functional analyses, including miRNet 2.0, were
performed, encompassing Co-DEmiRNA-gene, Co-DEmiRNA-transcription factor (TF),
and Co-DEmiRNA-compound networks. Functional enrichment analysis for Co-DEmiRNA
genes and Co-DEmiRNA-TF networks was conducted using KEGG, Reactome pathways,
and Gene Ontology (GO). Co-up and co-down DEmiRNAs were validated with TCGA
miRNA-seq data.
Results: hsa-mir-148a-3p, hsa-mir-148b-5p, and hsa-mir-623 are
the top miRNA nodes in Co-DEmiRNA-Target networks. The most significant
candidate miRNA dysregulation genes are POU2F1, TMOD3, SCD, PRRC2C, and MAT2A,
while the most important dysregulation TF includes TP53, CREB1, DNMT1, E2F1,
and EGR1. Arsenic trioxide, Gemcitabine, and
1,2,6-Tri-O-galloyl-beta-D-glucopyranose are the most correlated compounds.
Functional analyses revealed multiple cell signaling pathways such as NOTCH and
CREB phosphorylation, and regulation of processes such as RNA metabolism and
transcription.
Conclusions:
Our study
suggests candidate molecular mechanisms linking periodontitis to prostate
cancer, highlighting potential compounds targeting both diseases. These
findings provide a foundation for guiding future basic and clinical research.
KEYWORDS: Prostate
cancer, Periodontitis, Network analysis, MicroRNA, Genetic crosstalk.