Here we report that deletion of the mir-17~92 miRNA cluster results in the regression of KRASG12D-driven PanIN lesions and the expansion of normal acinar tissue in place of neoplastic cells over time. In addition, we observe that mir-17~92-null PanIN lesions have reduced ERK phosphorylation, and PanIN cell lines with ectopic mir-17~92 expression display elevated p-ERK levels. However, mir-17~92-null PanIN lesions display no changes in MEK phosphorylation or PI3K/AKT signaling, suggesting a specific impact of mir-17~92 on ERK activation. Importantly, apoptotic rates are not increased in mir-17~92-null PanINs, suggesting that these lesions are not lost by apoptosis. Moreover, the proliferation rate is unchanged in the adjacent acinar tissue of 17KC mice compared to that of KC mice, indicating that exocrine recovery is not due to the expansion of residual acinar cells in these animals. Together, these findings suggest that mir-17~92 loss promotes the redifferentiation of PanINs into acinar cells. While sophisticated lineage tracing experiments will be required to validate this hypothesis, our data are in agreement with recently published data demonstrating that ERK pathway activity downstream of KRASG12D is critical for PanIN maintenance, and loss of ERK signaling triggers PanIN regression into normally differentiated exocrine tissue . Importantly, the effects of miRNAs on signaling pathway output are generally smaller in magnitude than those observed with small molecule inhibitors, which potentially explains the extended timeline of PanIN regression in 17KC mice compared to the rapid regression described by Collins, et al. using MEK inhibitors .