Mapping the BRCA1 Protein Interaction Network: Functional Insights and Therapeutic Implications in Cancer
Oluwatobiloba Kehinde Adedokun
Department of Surgery, General Hospital Odan, Lagos, Nigeria.
Aliyu Olanrewaju Olaniyi
*
Department of Geriatric Medicine, Stockport NHS Foundation Trust, Stepping Hill Hospital, Stockport, Manchester, United Kingdom.
Happiness Ifedolapo Olaniyi
Nursing Unit, Barton Brook Nursing Home, Eccles, Manchester, M30 0GP, United Kingdom.
Basma Alleelwa
Acute Medical Unit, Stockport NHS Foundation Trust, Stepping Hill Hospital, Stockport, Manchester, United Kingdom.
*Author to whom correspondence should be addressed.
Abstract
Background: Breast Cancer Type 1 Susceptibility Protein (BRCA1) is an important tumour suppressor gene that plays a crucial role in preserving genomic stability through its involvement in DNA repair, chromatin remodelling, and transcription regulation. The risk of some diseases, such as breast and ovarian cancer, increases significantly when the BRCA1 gene is mutated. However, targeting the BRCA1 gene in cancer therapy has remained a significant challenge for scientists.
Objective: The study aims to explore the protein interaction network of BRCA1 to elucidate its functional associations and regulatory mechanisms, identify previously unrecognised therapeutic targets, and investigate the effect of PI3K-AKT inhibition on BRCA1.
Methods: The BRCA1 interaction network was constructed using the STRING database (v12.0) at a high-confidence interaction score (0.900). Clusters of proteins were obtained through K-means, and the main interactors were grouped into three levels by carrying out a thorough analysis through the Reactome pathway. Some common interactors were identified through frequency analysis. In order to uncover the biological processes related to the BRCA1 network, pathway enrichment was subsequently conducted.
Results and Discussion: This study elucidates the complex and highly regulated protein interaction network of BRCA1, revealing its pivotal role in multiple cellular pathways. The analysis identified key interactors, particularly within the PI3K-AKT signaling pathway, that may serve as promising therapeutic targets. BRCA1 was also found to function at the intersection of endocrine, hormonal, and metabolic regulation, underscoring its importance in maintaining tissue homeostasis. These findings highlight BRCA1’s potential as a target for integrated hormonal and metabolic therapies in BRCA1-associated cancers. Overall, this study provides insights that could advance the development of more effective diagnostic and therapeutic strategies to improve outcomes for individuals with BRCA-related malignancies.
Keywords: BRCA1, protein-protein interaction, STRING, Reactome, PI3K-AKT, DNA repair, synthetic lethality, bioinformatics