In-Silico Analysis of CDC۴۵ in Triple-Negative Breast Cancer progression

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer that makes up approximately ۱۰-۲۰% of all breast cancer cases. It is characterized by a lack of targeted therapies, which makes treatment challenging. CDC۴۵ (Cell Division Control Protein ۴۵) plays a crucial role in initiating chromosomal DNA replication, serving as an essential part of the CMG helicase complex that unwinds DNA during the replication process. In this study, the focus is on CDC۴۵ as a gene that is differentially expressed in TNBC cells, analyzed through bioinformatics tools and databases. Methods: The microarray dataset GSE۱۱۳۸۶۵ was obtained from the Gene Expression Omnibus (GEO) database for this analysis. Several bioinformatics platforms, including GEO۲R, GEPIA۲, and UALCAN, were employed to further examine and visualize the dataset. Furthermore, a list of ۱۰۰ significant differentially expressed genes (DEGs) was derived using the Limma package in R, applying thresholds of |LogFC| > ۲ and p-value < ۰.۰۵. Pathway enrichment analysis was performed using Reactome, and the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. Finally, TargetScan and miRWalk were utilized to identify and confirm the link between hsa-miR-۵۷۵ and the regulation of CDC۴۵ expression in TNBC cells. Results: The analysis showed that CDC۴۵ is remarkably overexpressed in TNBC cells when compared to normal breast tissue, indicating its potential role in driving tumor growth and progression. Moreover, additional research using TargetScan and miRWalk databases suggested that hsa-miR-۵۷۵ positively regulates CDC۴۵ expression in tumor cells. Pathway enrichment analysis through Reactome revealed that CDC۴۵, along with other genes such as CDC۲۰, UBE۲C, EXO۱, and CENPA, is involved in pathways associated with cell cycle checkpoints. Conclusion: The findings of this study highlight the importance of cell cycle checkpoints in the development and progression of TNBC. Targeting these pathways, particularly through the suppression of CDC۴۵ activity, could represent a novel therapeutic strategy for controlling TNBC growth. However, further in-silico and experimental studies are necessary to validate these findings and explore their potential clinical applications.

کلیدواژه ها:

TNBC ، CDC۴۵ ، Bioinformatics ، has_miR_۵۷۵