Unit:
Specialty Molecular Biomedicine Mechanisms of Disease, Molecular and Cellular Therapies, and BioinnovationLibrary of the School of Health Sciences
Supervisors info:
Απόστολος Κλινάκης, Ερευνητής Α', ΙΙΒΕΑΑ
Μαργαρίτης Αυγέρης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Θεόδωρος Ράμπιας, Ερευνητής Γ', ΙΙΒΕΑΑ
Original Title:
The role of KMT2C/MLL3 in oxidative DNA damage
Translated title:
The role of KMT2C/MLL3 in oxidative DNA damage
Summary:
Over the last decade the potential roles of enhancer mutations along with mutation of epigenetic regulators, such as KMT2C/MLL3 in cancer pathogenesis have been extensively studied. Thus, the role of epigenetic regulators in cancer initiation and progression is well established. Hence, researchers are now focusing on how our knowledge about epigenetic factors can be exploited therapeutically to target liabilities that arise from epigenetic dysregulation. Especially in bladder cancer, where there is an uncertainty regarding the optimal therapies that should be followed, patient’s stratification based on alterations on their epigenetic profile would be of a great value for patients’ quality of life and clinical outcome. With the aim of contributing to this goal, we studied the role of KMT2C/MLL3 H3K4 methyltransferase in oxidative DNA damage, following our observation that bladder cancer patients that bear KMT2C mutations are characterized by oxidative DNA damage signatures. We employed two human bladder cancer cell lines and examined the impact of KMT2C knockdown on their ROS levels, oxidative DNA damage and Base Excision Repair (BER) machinery functionality, which is responsible for oxidative DNA damage repair. We report that human bladder cancer KMT2C knockdown cells have high ROS levels that are also translated into oxidative DNA damage by means of 8-oxoG formation. Additionally, the expression of enzymes that participate into 8-oxoG repair have altered expression levels.
Main subject category:
Health Sciences
Keywords:
Bladder cancer, Epigenetics, MLL3, KMT2C, ROS, Oxidative stress, 8-oxoG, Base excision repair (BER)
File:
File access is restricted until 2025-11-24.
MSc Thesis-Ntounias.docx.pdf
2 MB
File access is restricted until 2025-11-24.
