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posted on 2025-03-03, 17:54 authored by Deniz Sünnetçi AkkoyunluDeniz Sünnetçi Akkoyunlu, Cansu UĞURTAŞ, Nurhan KÜLCÜ SARIKAYA, Tolgahan ÖZER, Naci ÇİNE, Seda EREN KESKİN, Aylin KANLIAylin KANLI, Hakan SAVLI

Background: Periodontitis is a prevalent multifactorial, oral infectious disease and is considered a high-risk factor for pancreatic cancer. Nevertheless, there is limited understanding of the underlying epigenetic mechanisms governing this relationship. The aim of this study was to identify dysregulated miRNAs associated with periodontitis and pancreatic cancer, along with their related genes, signaling pathways, and compounds. Material and Methods: miRNA expression datasets for tissues affected by periodontitis and pancreatic cancer were obtained from the Gene Expression Omnibus database. Differentially expressed miRNAs relative to the normal tissues were detected, and differentially expressed miRNAs common to both datasets were determined. Further bioinformatics approaches were used to explore the association of common differentially expressed miRNAs with periodontitis and pancreatic cancer. Results: Twenty shared, differentially expressed miRNAs were identified; 14 exhibited similar expression patterns in both diseases. Among these common differentially expressed miRNAs,10 were found to be overexpressed. Hsa-miR-155, hsa-miR-186, hsa-miR-765, hsa-miR-211 and hsa-miR-375were the top miRNA nodes in the gene network, with hsa-mir-155being the sole miRNA node in the transcription factor network. Top candidate miRNA-dysregulated genes included Superoxide Dismutase 2 (SOD2), Nuclear FMR1 Interacting Protein 2 (NUFIP2), SFT2 Domain Containing 2 (SFT2D2), Thioredoxin Interacting Protein (TXNIP), and Cyclin D1 (CCND1), while top dysregulated transcription factors were Argonaute RISC Catalytic Component 2 (AGO2), AKT Serine/Threonine Kinase 1 (AKT1), B-Cell Lymphoma 6 (BCL6), Breakpoint Cluster Region (BCR), and BRCA1 DNA Repair Associated (BRCA1). Relevant compounds for targeting these emerged, including 5-fluorouracil, gemcitabine, doxorubicin, ascorbate, diethylstilbestrol, and temozolomide. Conclusion: Our study suggests candidate molecular mechanisms linking periodontitis to pancreatic cancer, highlighting potential compounds that may target both diseases. These findings provide a foundation for guiding future fundamental and clinical research.

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