Kanli Aylin, Sunnetci-Akkoyunlu Deniz, Kulcu-Sarikaya Nurhan, Ugurtaş Cansu, Akpinar Gurler, Kasap Murat
Department of Medical Biology, Kocaeli University Faculty of Medicine, Kocaeli, Turkiye;
Department of Medical Genetics, Kocaeli University Faculty of Medicine, Kocaeli, Turkiye.
In Vivo. 2025 Mar-Apr;39(2):795-809. doi: 10.21873/invivo.13863.
BACKGROUND/AIM: Prostate cancer 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.
The miRNA expression datasets of prostate cancer and periodontitis were obtained 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.
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.
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.
背景/目的：前列腺癌是男性癌症相关死亡的第二大主要原因。牙周炎被认为是前列腺癌的一个高危因素，但其遗传机制尚不清楚。本研究旨在确定失调的miRNA、它们的相关基因、信号通路以及将牙周炎与前列腺癌联系起来的化合物。
从GEO数据库中获取前列腺癌和牙周炎的miRNA表达数据集。鉴定差异表达的miRNA（DEmiRNA），并确定两个数据集之间的共同DEmiRNA（Co-DEmiRNA）。进行了Co-DEmiRNA-靶标网络结构和功能分析，包括miRNet 2.0，涵盖Co-DEmiRNA-基因、Co-DEmiRNA-转录因子（TF）和Co-DEmiRNA-化合物网络。使用KEGG、Reactome通路和基因本体（GO）对Co-DEmiRNA基因和Co-DEmiRNA-TF网络进行功能富集分析。通过TCGA miRNA-seq数据验证共上调和共下调的DEmiRNA。
hsa-mir-148a-3p、hsa-mir-148b-5p和hsa-mir-623是Co-DEmiRNA-靶标网络中的顶级miRNA节点。最显著的候选miRNA失调基因是POU2F1、TMOD3、SCD、PRRC2C和MAT2A，而最重要的失调TF包括TP53、CREB1、DNMT1、E2F1和EGR1。三氧化二砷、吉西他滨和1,2,6-三-O-没食子酰-β-D-吡喃葡萄糖是最相关的化合物。功能分析揭示了多种细胞信号通路，如NOTCH和CREB磷酸化，以及RNA代谢和转录等过程的调控。
我们的研究提出了将牙周炎与前列腺癌联系起来的候选分子机制，突出了针对这两种疾病的潜在化合物。这些发现为指导未来的基础和临床研究提供了基础。
