Given its rate of mutational activation in PDAC and past observations of oncogene addiction, KRAS and components of its downstream signaling pathways represent robust therapeutic targets in this devastating malignancy. To date, efforts to directly inhibit KRAS function have been unsuccessful ; thus efforts in the field have turned to targeting key downstream pathways [9–11]. However, a deeper understanding of the mechanisms responsible for the transforming effect of KRAS could inform more effective therapeutic strategies. Several microRNAs, including those in the mir-17~92 cluster, display increased expression in PDAC as well as precursor PanIN lesions [22–24], suggesting that these miRNAs may play a role in tumorigenesis. However, to date, the functional importance of these miRNAs has not been evaluated in vivo.