Abstract 1378: The histone methyltransferase adaptor WDR5 is a novel cofactor in neuroblastoma

Abstract

Abstract Introduction: Neuroblastoma is the most common extracranial solid malignancy in early childhood. WDR5 is an essential component of the MLL and SET1/COMPASS histone H3 lysine 4 (H3K4) methyltransferase complex and plays a key role in the trimethylation of H3K4. However, there is no previous study establishing the role of WDR5 in neuroblastoma. Results: Affymetrix gene array studies showed that knocking-down WDR5 expression with siRNAs reduced the expression of the cell cycle genes cyclin E1. Consistently, RT-PCR and immunoblot confirmed that WDR5 siRNAs reduced cyclin E1 mRNA and protein expression, ChIP assays showed that WDR5 siRNAs reduced histone H3K4 tri-methylation at the cyclin E1 gene promoter, and Alamar blue assays demonstrated that WDR5 induced neuroblastoma cell proliferation. Additionally, high levels of WDR5 gene expression in human neuroblastoma tissues predict poor patient survival independent of patient age and disease stage. Conclusions: Our data demonstrate WDR5 as a novel co-factor in neuroblastoma oncogenesis, and provide critical evidence to support the application of WDR5 inhibitors for the therapy of neuroblastoma patients. Citation Format: Yuting Sun, Pei Yan Liu, Daniel Carter, Nicolas Sokolowski, Karen L. MacKenzie, Glenn M. Marshall, Tao Liu. The histone methyltransferase adaptor WDR5 is a novel cofactor in neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1378. doi:10.1158/1538-7445.AM2014-1378