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Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics
Gintoni, I.; Vassiliou, S.; Chrousos, G.P.; Yapijakis, C. Identification of Stage-Specific microRNAs that Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Human Genetics with Epigenetics and Utilizing an Animal Model. Int. J. Mol. Sci.2024, 25, 7642.
Gintoni, I.; Vassiliou, S.; Chrousos, G.P.; Yapijakis, C. Identification of Stage-Specific microRNAs that Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Human Genetics with Epigenetics and Utilizing an Animal Model. Int. J. Mol. Sci. 2024, 25, 7642.
Gintoni, I.; Vassiliou, S.; Chrousos, G.P.; Yapijakis, C. Identification of Stage-Specific microRNAs that Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Human Genetics with Epigenetics and Utilizing an Animal Model. Int. J. Mol. Sci.2024, 25, 7642.
Gintoni, I.; Vassiliou, S.; Chrousos, G.P.; Yapijakis, C. Identification of Stage-Specific microRNAs that Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Human Genetics with Epigenetics and Utilizing an Animal Model. Int. J. Mol. Sci. 2024, 25, 7642.
Abstract
Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.
Keywords
Oral squamous cell carcinoma; OSCC; oral cancer; miRNA; miRNA expression; genes; gene expression; hyperplasia; dysplasia; early invasion; early stage OSCC; in situ carcinoma; precancerous lesions; animal model; early diagnosis; liquid biopsy
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
