The oncogenic K-Ras can transform various mammalian cells and plays a critical
role in development of pancreatic cancer. MicroRNAs (miRNA) have been shown to
contribute to tumorigenic progression. However, the nature of miRNAs involved
in K-Ras transformation remains to be investigated. Here, by using microarray we
identified miR-155 as the most upregulated miRNA after both acute and prolonged
activation of K-Ras in a doxycyline-inducible system. Pharmacological inhibition of
MAPK and NF-κB pathway blocked the induction of miR-155 in response to K-Ras
activation. Overexpression of miR-155 caused inhibition of Foxo3a, leading to
decrease of major antioxidants including SOD2 and catalase, and enhanced pancreatic
cell proliferation induced by ROS generation. Importantly, correlations of K-Ras, miR-
155 and Foxo3a were also validated in human pancreatic cancer tissues. Therefore,
we propose that miR-155 plays an important role in oncogenic K-Ras transformation
mediated by cellular redox regulation.