The RNA binding protein QKI guides a pro-mesenchymal splicing program driving a subtype switch and limiting outcome in pancreatic cancer [PANC-1 and HPAF-II]

Transcriptomic analyses have identified two molecular PDAC subtypes, one of which, namely basal-like subtype, is associated with chemoresistance and worse clinical outcomes. Splicing dysregulation is known to contribute to PDAC malignancy. Functional studies in PDAC cells lines identified the splicing factor QKI as a key determinant of a basal-like splicing signature associated with increased tumor aggressiveness. Our studies demonstrate that QKI represses splicing events associated with the classical subtype and improved clinical outcome, while promoting basal-like events associated with shorter survival. Briefly, PANC-1 cells were silenced for QKI and RBFOX2 (40nM) for 48 hours.HPAF-II cell silenced with siCtrl. Each samples has 3 biological replicates.