Transcritpional response of human neuroblastoma cells treated with EHMT and EZH2 inhibitors

MYCN-amplified neuroblastomas are characterized by an non-inflamed immune phenotype. N-Myc is involved in the suppression of immune signaling pathways such as the interferon pathways. We tested the idea that epigentic modifiers could be attractive drug targets to restore interferon signaling activity in human neuroblastoma cells. Transcriptome analyses led to the identification of euchromatic histone-lysine methyltransferases (EHMTs) as potential suppressors of interferon signaling in neuroblastoma cells. Pharmacological approches using small molecule inhibitors confirmed that inhibition of EHMTs enhanced transcriptional responses to infereron-gamma. This effect was augmented by co-inhibition of EZH2 (enhancer of zeste 2 homolog). For our study, we treated SK-N-BE and IMR-32 MYCN-amplified human neuroblastoma cells with EHMT, EZH2 or both types of inhibitors and studied transcriptional responses to interferon gamma. RNA-seq was done by using a 3'mRNA-Seq approach.