PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics
Version 1
: Received: 23 May 2024 / Approved: 24 May 2024 / Online: 24 May 2024 (08:38:17 CEST)
How to cite:
Gintoni, I.; Vassiliou, S.; Chrousos, G.; Yapijakis, C. Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics. Preprints2024, 2024051606. https://doi.org/10.20944/preprints202405.1606.v1
Gintoni, I.; Vassiliou, S.; Chrousos, G.; Yapijakis, C. Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics. Preprints 2024, 2024051606. https://doi.org/10.20944/preprints202405.1606.v1
Gintoni, I.; Vassiliou, S.; Chrousos, G.; Yapijakis, C. Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics. Preprints2024, 2024051606. https://doi.org/10.20944/preprints202405.1606.v1
APA Style
Gintoni, I., Vassiliou, S., Chrousos, G., & Yapijakis, C. (2024). Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics. Preprints. https://doi.org/10.20944/preprints202405.1606.v1
Chicago/Turabian Style
Gintoni, I., George Chrousos and Christos Yapijakis. 2024 "Identification of Stage-Specific microRNAs That Govern the Early Stages of Sequential Oral Oncogenesis by Strategically Bridging Genetics and Epigenetics" Preprints. https://doi.org/10.20944/preprints202405.1606.v1
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.
