Journal article

Genome-wide functional genomic and transcriptomic analyses for genes regulating sensitivity to vorinostat

Katrina J Falkenberg, Cathryn M Gould, Ricky W Johnstone, Kaylene J Simpson



Identification of mechanisms of resistance to histone deacetylase inhibitors, such as vorinostat, is important in order to utilise these anticancer compounds more efficiently in the clinic. Here, we present a dataset containing multiple tiers of stringent siRNA screening for genes that when knocked down conferred sensitivity to vorinostat-induced cell death. We also present data from a miRNA overexpression screen for miRNAs contributing to vorinostat sensitivity. Furthermore, we provide transcriptomic analysis using massively parallel sequencing upon knockdown of 14 validated vorinostat-resistance genes. These datasets are suitable for analysis of genes and miRNAs involved in cell death in t..

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Awarded by Australian National Health and Medical Research Council (NHMRC)

Funding Acknowledgements

We thank Richard Tothill, Maria Doyle and Jason Ellul for constructive discussions about NGS methodologies and analysis. For technical support, we thank Yanny Handoko and Daniel Thomas (Victorian Centre for Functional Genomics) and Timothy Semple, Timothy Holloway and Aga Borcz (Molecular Genomics Facility). This work was supported by Merck Sharp and Dohme, and an Australian National Health and Medical Research Council (NHMRC) project grant APP1028871 (to RWJ). KJF was a recipient of an Australian Postgraduate Award and later a Cancer Council Victoria Postdoctoral Research Fellowship. RWJ is a Principal Research Fellow of the National Health and Medical Research Council (NHMRC) of Australia and supported by NHMRC Program and Project Grants, Cancer Council Victoria, the Leukaemia Foundation of Australia, and the Victorian Cancer Agency. The VCFG (KJS) is funded by the Australian Cancer Research Foundation (ACRF), the Victorian Department of Industry, Innovation and Regional Development (DIIRD), the Australian Phenomics Network (APN) supported by funding from the Australian Government's Education Investment Fund through the Super Science Initiative, the Australasian Genomics Technologies Association (AMATA), the Brockhoff Foundation and the Peter MacCallum Cancer Centre Foundation.