Targeting SWI/SNF ATPases reduces cell invasiveness and plasticity in core transcription factors-addicted neuroblastoma [RNA-seq]

Neuroblastoma (NB) comprises mesenchymal (MES) and adrenergic (ADRN) subtypes, and the cell identity is determined by core transcription factors (TFs). However, the binding mechanism of these TFs to DNA and the epigenetic mechanisms governing NB plasticity remain unclear. In this study, we investigated the impact of targeting SWI/SNF ATPases with SMARCA2/4 dual degraders on NB cells. Our results revealed that depletion of SWI/SNF ATPases compacted cis-regulatory elements, diminished enhancer activity, and displaced core TFs (MYCN, HAND2, PHOX2B, and GATA3) from DNA, suppressing transcriptional programs linked to plasticity and invasiveness. These findings underscore the pivotal role of SWI/SNF ATPases in driving NB progression, positioning them as promising therapeutic targets. To investigate the effect of SWI/SNF ATPases depletion on gene expression in NB cells, we treated different NB cell lines with or without ACBI1 for 8, 24 or 96 hours, or transfected NB cells with control siRNA (siCtrl) or two different SMARCA4 siRNAs (siSMA4-5, siSMA5-7) for 48 hours. RNA-seq was performed for gene expression profiling analysis.