KDM1A inhibition is effective in reducing stemness and treating triple negative breast cancer

We examined the transcriptional changes modulated by lysine-specific histone demethylase 1 (KDM1A/LSD1) by perfroming global transcriptome analysis. MDA-MB-231 cancer stem cells (CSCs) were transduced with control shRNA or KDM1A shRNA lentiviral particles and the RNA was isolated and utilized for RNA-seq analysis. Our results demonstrated that differentially expressed genes were enriched in biological processes of regulation of organismal processes, cell migration, cell motility, cell proliferation and cell differentiation. In terms of molecular function, the differentially expressed genes were enriched in growth factor activity, cytokine activity, and cytokine receptor binding. Importantly, GSEA results demonstrated that KDM1A regulated genes showed a negative correlation with the gene sets of IL6-JAK-STAT3 signaling and epithelial mesenchymal transition (EMT) pathways. Overall design: Total RNA was isolated from MDA-MB-231 CSCs expressing either control shRNA or KDM1A shRNA. Illumina TruSeq RNA Sample Preparation was performed following manufacturer's protocol. Samples were run on an Illumina HiSeq 3000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.