Pluto Bioinformatics

GSE67681: HDAC Inhibition Impedes HMGA2-controlled Epithelial-Mesenchymal Plasticity and Suppresses Metastatic, Castration-Resistant Prostate Cancer (RNA-seq)

Bulk RNA sequencing

To study the dynamic regulation of the Epithelial-Mesenchymal Transition (EMT), we developed genetically-defined cellular and in vivo model systems from which Epithelial, EMT, and Mesenchymal-like tumor cells can be isolated. When cultured individually, each population has the plasticity to generate all three populations, implying epigenetic regulation of the EMT program. Among differentially expressed epigenetic regulators, HMGA2 is significantly upregulated in EMT and Mesenchymal-like tumors cells, as well as in human metastatic castration-resistant prostate cancer (mCRPC). Knockdown of Hmga2, or suppressing Hmga2 expression with the HDAC inhibitor LBH589, inhibits EMT and stemness activities in vitro and dramatically reduces prostate tumor burden and distant metastasis in vivo. Importantly, LBH589 in combination with castration significantly prolongs survival by impeding the onset of mCRPC. SOURCE: Yu-Ting TsengXing Lab University of California, Los Angeles