Computational insights into irinotecan's interaction with UBE2I in ovarian and endometrial cancers

Tamizhini Loganathan; Madhulekha S; Hatem Zayed; George Priya Doss C

doi:10.1016/j.compbiolchem.2024.108250

Computational insights into irinotecan's interaction with UBE2I in ovarian and endometrial cancers

Comput Biol Chem. 2024 Oct 16:113:108250. doi: 10.1016/j.compbiolchem.2024.108250. Online ahead of print.

Authors

Tamizhini Loganathan¹, Madhulekha S², Hatem Zayed³, George Priya Doss C⁴

Affiliations

¹ Laboratory of Integrative Genomics, Department of Integrative Biology, School of BioSciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India. Electronic address: tamizhini.l2021@vitstudent.ac.in.
² Laboratory of Integrative Genomics, Department of Integrative Biology, School of BioSciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India. Electronic address: madhulekhas19@gmail.com.
³ Department of Biomedical Sciences College of Health Sciences, QU. Health, Qatar University, Doha, Qatar. Electronic address: hatem.zayed@qu.edu.qa.
⁴ Laboratory of Integrative Genomics, Department of Integrative Biology, School of BioSciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India. Electronic address: georgepriyadoss@vit.ac.in.

PMID: 39476484
DOI: 10.1016/j.compbiolchem.2024.108250

Abstract

Endometrial and Ovarian cancers are two highly prevalent and fatal reproductive diseases with poor prognoses among women. Elevated estrogen levels in Ovarian Cancer (OC) stimulate the endometrium, causing Endometrial Cancer (EC). Although numerous studies have reported the crucial genes and pathways in this cancer, the pathogenesis of this disease remains unclear. In this study, used bioinformatics tools to analyse GSE63678, GSE115810, GSE36389, GSE26712, GSE36668, GSE27651, GSE6008, GSE69429, GSE69428, GSE18521, GSE185209, GSE54388 gene expression microarray datasets for both the cancers. We analyzed the differential gene expression, functional association, and structural studies. The analysis identified crucial differentially expressed genes (DEGs) in both cancers associated with DNA damage, DNA integrity, and cell-cycle checkpoint signaling pathways. CLDN7, UBE2I, WT1, JAM2, FOXL2, F11R, JAM3, ZFPM2, MEF2C, and PIAS1 are the top 10 hub genes commonly identified in both cancer types. Only CLDN7 and F11R are upregulated, whereas the remaining hub genes are downregulated in both cancers, suggesting a common framework for contributing to tumorigenesis. Molecular docking and dynamics were performed on the UBE2I protein with Irinotecan Hydrochloride, which could serve as the new approach for treating and managing both cancers. The study reveals the common molecular pathways, pointing out the role of cell cycle and DNA damage and integrity checkpoint signaling in the pathogenesis of both cancer types. This study explored the UBE2I gene as a potential biomarker in OC and EC. Further, this study concludes that the irinotecan hydrochloride drug has higher therapeutic effects on UBE2I protein through docking and dynamics studies.

Keywords: Endometrial cancer and UBE2I; Ovarian cancer.