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Figure S1-S6, Table S1-S2 from Targeting Histone Demethylases in MYC-Driven Neuroblastomas with Ciclopirox

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posted on 2023-03-31, 00:41 authored by 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

Figure S1 shows siRNA screening in neuroblastoma cells. Figure S2 shows the dentification of ciclopirox that targets KDM4B. Figure S3 shows the CPX effect on other histone methyl marks. Figure S4 shows that CPX targets the Myc pathway. Figure S5 shows that CPX inhibits oxidative phosphorylation. Figure S6 shows the CPX effect on BE2C xenografts with KDM4B knockdown. Table S1 shows the sequences of the focused KDM siRNA library. Table S2 shows the primers for real time PCR.

Funding

Assisi Foundation of Memphis

National Cancer Institute

American Lebanese Syrian Associated Charities

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ARTICLE 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.

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    Cancer Research

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    Drug TargetsEpigeneticsPediatric CancersSmall Molecule Agents

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