SNW1 regulates Notch signaling in neuroblastoma through interacting with RBPJ

Abstract

The Notch signaling pathway is highly conserved, involved in cell-cell communication, and essential for multicellular organism development. The recombination signal binding protein for immunoglobulin kappa J region (RBPJ) transcriptional regulator plays a vital role in Notch signaling. When not complexed with Notch proteins, RBPJ acts as a transcriptional repressor. However, when bound to the Notch intracellular domain (NOTCH ICD) in the nucleus, RBPJ activates the transcription of Notch target genes. However, the role of RBPJ in the Notch signaling pathway in neuroblastoma (NB) remains unclear. In this study, we show that SNW domain containing 1 (SNW1) acts as a novel RBPJ partner and regulates the expression of Notch target genes. Additionally, we show that silencing RBPJ expression can prevent SNW1-mediated Notch gene expression. Public datasets and clinical NB tissues indicate that RBPJ and SNW1 are upregulated in NB, and are associated with unfavorable patient outcomes. Taken together, our results highlight that SNW1 interacts with RBPJ to regulate the Notch signaling pathway and presents a potential therapeutic target for NB.