Histone Demethylase (KDM3A) Regulation and Its Impact on Estrogen Receptor-Positive Breast Cancer Progression

The histone demethylase-encoding gene KDM3A is a crucial modulator of estrogen receptor (ER) signaling, impacting the development of ER-positive breast cancer.Resistance develops despite the effectiveness of endocrine drugs that target ER signaling, necessitating a deeper understanding of the underlying molecular processes.This work investigated KDM3A depletion in ER-positive breast cancer cells to gain a better understanding of how it impacts estrogen-induced gene expression and its potential as a therapeutic target in endocrine-resistant breast cancer.We used the GEO dataset GSE68918, which contains gene expression profiles from MCF-7 cell lines treated with KDM3A RNA (siKDM3A) and scrambled RNA (siSCR), to find 845 differentially expressed genes (DEGs).Following KDM3A knockdown, 402 of these genes showed upregulation, and 444 showed downregulation.Significant downregulation was observed for BRCA1 and CCNB1, but a notable upregulation was observed for CEACAM6.This suggests that KDM3A is involved in signaling through estrogen receptors, repairing DNA, and regulating the cell cycle.A study of protein-protein interaction (PPI) networks showed that hub genes, including TOP2A, CCNA2, and CCNB1, are essential for KDM3A-related networks.Significant enrichment in the p53 signaling pathway, DNA replication, and cell division was found by Gene Ontology (GO) and KEGG pathway studies, highlighting the influence of KDM3A on important biological processes.These findings suggest that KDM3A could be a valuable therapeutic target in the management of breast cancer endocrine resistance.Future research should look at the therapeutic potential of KDM3A inhibitors to enhance the efficacy of treatment for endocrine-resistant breast cancer, particularly when combined with other forms of therapy.