Single-Cell Sequencing Identifies Master Regulators Affected by Panobinostat in Neuroblastoma Cells

The molecular mechanisms and gene regulatory networks sustaining cell proliferation in neuroblastoma (NBL) cells are still not fully understood. In this tumor context, it has been proposed that anti-proliferative drugs, such as the pan-HDAC inhibitor panobinostat, could be tested to mitigate tumor progression. Here, we set out to investigate the effects of panobinostat treatment at the unprecedented resolution offered by single-cell sequencing. We identified a global senescence signature paired with reduction in proliferation in treated Kelly cells and more isolated transcriptional responses compatible with early neuronal differentiation. Using master regulator analysis, we identified BAZ1A, HCFC1, MAZ, and ZNF146 as the transcriptional regulators most significantly repressed by panobinostat. Experimental silencing of these transcription factors (TFs) confirmed their role in sustaining NBL cell proliferation in vitro.

Automated summary

This study identified a global senescence signature and reduced proliferation in NBL cells treated with panobinostat, as well as transcriptional responses compatible with early neuronal differentiation. Through master regulator analysis, BAZ1A, HCFC1, MAZ, and ZNF146 were identified as the transcriptional regulators most significantly repressed by panobinostat, and experimental silencing confirmed their role in sustaining NBL cell proliferation in vitro.