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Inhibition of Aurora Kinase Induces Endogenous Retroelements to Induce a Type I/III IFN Response via RIG-I

Cancer Res Commun. 2024-02; 
Lisa Choy, Stephen Norris, Xiumin Wu, Ganesh Kolumam, Ari Firestone, Jeffrey Settleman, David Stokoe
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Codon Optimization … gene (Genscript). We introduced a silent C→T mutation located 28 bp upstream of the IFI27 STOP codon in the left homology arm, to destroy the PAM site following the guide sequence (… Get A Quote

摘要

unlabelled: Type I IFN signaling is a crucial component of antiviral immunity that has been linked to promoting the efficacy of some chemotherapeutic drugs. We developed a reporter system in HCT116 cells that detects activation of the endogenous IFI27 locus, an IFN target gene. We screened a library of annotated compounds in these cells and discovered Aurora kinase inhibitors (AURKi) as strong hits. Type I IFN signaling was found to be the most enriched gene signature after AURKi treatment in HCT116, and this signature was also strongly enriched in other colorectal cancer cell lines. The ability of AURKi to activate IFN in HCT116 was dependent on MAVS and RIG-I, but independent of STING, whose signaling is defi... More

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