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