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A forward genetics screen identifies modifiers of Rocaglate responsiveness

ABSTRACT: Rocaglates are a class of eukaryotic translation initiation inhibitors that are being explored as chemotherapeutic agents. They function by targeting eukaryotic initiation factor (eIF) 4A, an RNA helicase critical for recruitment of the 40S ribosome (and associated factors) to mRNA templates. To appreciate how rocaglates could best be enabled in the clinic, an understanding of resistance mechanisms is important, as this could inform on strategies to bypass such events as well as responsive tumor types. In performing a forward genetics screen using a cDNA library, we identified FOXP3 to be a gene of interest. As FOXP3 is a known transcriptional regulator, understandings its impacts on the transcriptional landscape was a logical undertaking in elucidating the resistance mechanis. Here, we report on the RNAseq results in Hap1 cells overexpressing FOXP3 compared to a negative control cell line expressing GFP. We find that certain genes involved in response to drug, such as ABCB1 (P-glycoprotein), are potently upregulated in a FOXP3-overexpression setting.

ORGANISM(S): Homo sapiens

PROVIDER: GSE167242 | GEO | 2021/09/22

REPOSITORIES: GEO

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