Unknown,Transcriptomics,Genomics,Proteomics

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RNA-seq analysis of vorinostat-resistant HCT116 cells following gene knockdown of GLI1 or PSMD13 with or without vorinostat treatment


ABSTRACT: Transcriptome analysis was conducted on vorinostat resistant HCT116 cells (HCT116-VR) upon knockdown of potential vorinostat resistance candidate genes in the presence and absence of vorinostat. Potential vorinostat resistance candidate genes chosen for this study were GLI1 and PSMD13, which were identified through a genome-wide synthetic lethal RNA interference screen. To understand the transcriptional events underpinning the effect of GLI1 and PSMD13 knockdown (sensitisation to vorinostat-induced apoptosis), cells were first subjected to gene knockdown, then to treatment with vorinsotat or the solvent control. Two timepoints for drug treatment were assessed: a timepoint before induction of apoptosis (4hrs for siGLI1 and 8hrs for siPSMD13) and a timepoint when apoptosis could be detected (8hrs for siGLI1 and 12hrs for siPSMD13). There are 42 samples in total, from triplicate independent biological experiments of 14 samples each.

ORGANISM(S): Homo sapiens

SUBMITTER: Katrina Falkenberg 

PROVIDER: E-GEOD-57871 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity.

Falkenberg K J KJ   Newbold A A   Gould C M CM   Luu J J   Trapani J A JA   Matthews G M GM   Simpson K J KJ   Johnstone R W RW  

Cell death and differentiation 20160212 7


Vorinostat is an FDA-approved histone deacetylase inhibitor (HDACi) that has proven clinical success in some patients; however, it remains unclear why certain patients remain unresponsive to this agent and other HDACis. Constitutive STAT (signal transducer and activator of transcription) activation, overexpression of prosurvival Bcl-2 proteins and loss of HR23B have been identified as potential biomarkers of HDACi resistance; however, none have yet been used to aid the clinical utility of HDACi.  ...[more]

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