Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Biochem Biophys Res Commun. 2019 Feb 19;509(4):869-876. doi: 10.1016/j.bbrc.2019.01.036. Epub 2019 Jan 12.
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.
Notch 信号通路高度保守，参与细胞间通讯，对多细胞生物的发育至关重要。免疫球蛋白 κ J 区重组信号结合蛋白（RBPJ）转录调节剂在 Notch 信号通路中起着至关重要的作用。当不与 Notch 蛋白结合时，RBPJ 作为转录抑制剂。然而，当与核内 Notch 细胞内结构域（NOTCH ICD）结合时，RBPJ 激活 Notch 靶基因的转录。然而，RBPJ 在神经母细胞瘤（NB）中的 Notch 信号通路中的作用尚不清楚。在这项研究中，我们表明 SNW 结构域包含 1（SNW1）作为一种新型的 RBPJ 伴侣，调节 Notch 靶基因的表达。此外，我们表明沉默 RBPJ 的表达可以阻止 SNW1 介导的 Notch 基因表达。公共数据集和临床 NB 组织表明，RBPJ 和 SNW1 在 NB 中上调，并与不良的患者预后相关。综上所述，我们的研究结果表明 SNW1 与 RBPJ 相互作用，调节 Notch 信号通路，并为 NB 提供了一个潜在的治疗靶点。
