Data from Targeting Histone Demethylases in MYC-Driven Neuroblastomas with Ciclopirox
Year: 2023
Type: other
Abstract: Histone lysine demethylases facilitate the activity of oncogenic transcription factors, including possibly MYC. Here we show that multiple histone demethylases influence the viability and poor prognosis of neuroblastoma cells, where MYC is often overexpressed. We also identified the approved small-molecule antifungal agent ciclopirox as a novel pan-histone demethylase inhibitor. Ciclopirox targeted several histone demethylases, including KDM4B implicated in MYC function. Accordingly, ciclopirox inhibited Myc signaling in parallel with mitochondrial oxidative phosphorylation, resulting in suppression of neuroblastoma cell viability and inhibition of tumor growth associated with an induction of differentiation. Our findings provide new insights into epigenetic regulation of MYC function and suggest a novel pharmacologic basis to target histone demethylases as an indirect MYC-targeting approach for cancer therapy. Cancer Res; 77(17); 4626–38. ©2017 AACR.
Authors: Jun Yang, Sandra Milasta, Dongli Hu, Alaa M. AlTahan, Rodrigo B. Interiano, Junfang Zhou, Jesse Davidson, Jonathan Low, Wenwei Lin, Ju Bao, Pollyanna Goh, Amit C. Nathwani, Ruoning Wang, Yingdi Wang, Su Sien Ong, Vincent A. Boyd, Brandon Young, Sourav Das, Anang Shelat, Yinan Wu, Zhenmei Li, Jie J. Zheng, Ashutosh Mishra, Yong Cheng, Chunxu Qu, Junmin Peng, Douglas R. Green, Stephen White, R. Kiplin Guy, Taosheng Chen, Andrew M. Davidoff
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361236843