Integrative Genomic and in Silico Analysis Reveals Mitochondrially Encoded Cytochrome C Oxidase III (MT—CO3) Overexpression and Potential Neem-Derived Inhibitors in Breast Cancer

作者：Oluwaseun E. Agboola, Samuel S Agboola, O. M. Oyinloye, Abimbola E. Fadugba, Esther Y. Omolayo, Zainab A. Ayinla, F. Osunsanmi, O. Olaiya, F. O. Olojo, B. Ajiboye, B. Oyinloye · 发表于：Genes · 年份：2025 · DOI：10.3390/genes16050546 · 被引用次数：16 · 研究领域：Medicine

Background: The increasing global incidence of breast cancer calls for the identification of new therapeutic targets and the assessment of possible neem-derived inhibitors by means of computational modeling and integrated genomic research. Methods: Originally looking at 59,424 genes throughout 42 samples, we investigated gene expression data from The Cancer Genome Atlas—Breast Cancer (TCGA-BRCA) dataset. We chose 286 genes for thorough investigation following strict screening for consistent expression. R’s limma package was used in differential expression analysis. The leading candidate’s protein modeling was done with Swiss-ADME and Discovery Studio. Molecular docking studies, including 132 neem compounds, were conducted utilizing AutoDock Vina. Results: Among the 286 examined, mitochondrially encoded cytochrome C oxidase III (MT—CO3) turned out to be the most greatly overexpressed gene, showing consistent elevation across all breast cancer samples. Protein modeling revealed a substantial hydrophobic pocket (volume: 627.3 Å3) inside the structure of MT—CO3. Docking investigations showed five interesting neem-derived inhibitors: 7-benzoylnimbocinol, nimolicinol, melianodiol, isonimocinolide, and stigmasterol. Strong binding affinities ranging from −9.2 to −11.5 kcal/mol and diverse interactions with MT—CO3, mostly involving the residues Phe214, Arg221, and Trp58, these molecules displayed. With hydrophobic interactions dominant across all chemicals, fragment contribution anal...