Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Ιωάννης Γ. Παναγιωτίδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Καβατζάς, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σωτήριος Τσιόδρας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Διαμάντω Ψυρρή, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Περικλής Γ. Φούκας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αλέξανδρος Δελίδης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πατέρας Ιωάννης, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μοριακή διερεύνηση της έκφρασης των miRNAs που ρυθμίζουν το ανοσιακό μονοπάτι PD-1/PD L-1 σε προκαρκινικές αλλοιώσεις και καρκινώματα τραχήλου μήτρας
Translated title:
Molecular investigation of the expression of miRNAs regulating the PD-1/PD L-1 immune pathway in precancerous lesions and cervical carcinomas
Summary:
Cervical cancer ranks third among all cancers in women worldwide. Immune checkpoints are networks of inhibitory and stimulatory pathways that support immune response and sustain self-tolerance. Immune checkpoint mechanisms are frequently triggered in cancer to block the development of anti-tumor immune responses. Programmed cell death protein 1 (PD-1) is a transmembrane protein and Its ligand (PDL-1) is usually expressed by macrophages, some activated T cells, B cells, dendritic cells, and epithelial cells under inflammatory conditions. It is also expressed by tumor cells in order to avoid anti-tumor immune responses. PD-1/PDL1 launches self-tolerance by downregulating the immune system’s response and by suppressing T-cell inflammatory activity. In this study, computationally predicted miRNAs that according to specific algorithm-based online tools bind to the 3’ UTR of PDL-1 mRNA were chosen, and their expression profile on formalin-fixed paraffin-embedded (FFPE) clinical samples of different histological categories was explored. The initial hypothesis was that if the studied miRNAs are capable of targeting PDL-1 mRNA and subsequently inhibiting its production, downregulation of studied miRNAs in high-grade lesions could be one of the reasons that PDL-1 is overexpressed, thus suggesting possible potential powerful candidates for therapeutic intervention. Among the studied miRNAs, hsa-Mir-125-5p was found to be significantly underexpressed in high-grade lesions, prompting further investigation into its potential involvement in the molecular pathway that includes the E6 oncogene of HPV16 and the PD-L1 protein. By applying the CRISPR/Cas9 system to cell line models, it was demonstrated that a decrease in E6 expression leads to an increase in hsa-Mir-125-5p expression and a reduction in PD-L1 protein levels. This suggests a molecular pathway where the presence of HPV16 may function to modulate hsa-Mir-125-5p and, specifically, its effect on the PD-L1 protein.
Main subject category:
Health Sciences
Keywords:
PD-1, miRNA, Cervical cancer
Number of references:
200
File:
File access is restricted until 2025-08-07.
ΔΙΔΑΚΤΟΡΙΚΟ_ΛΕΒΕΝΤΑΚΟΥ ΔΑΝΑΗ.pdf
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File access is restricted until 2025-08-07.
