Oleuropein inhibits pancreatic cancer through miR-190b-5p induction

Background: Pancreatic cancer has the highest mortality rate of all major cancers. Till now, surgical resection is considered the only potentially curative therapy. The aim of this study was to study oleuropein (Ole) as an alternative treatment for pancreatic cancer. Methods: First, we determined the tumor-inhibitory effect of Ole in pancreatic cancer cell lines and the KPC mouse model. Second, we employed microarray and real-time polymerase chain reaction to identify microRNAs (miRNA) regulated by Ole in pancreatic cancer. Third, we mapped out the downstream target of the miRNA candidate by luciferase assay and western blotting. Finally, we measured the tissue expression of the miRNA candidate in clinical samples. Both in vitro and in vivo studies supported Ole treatment suppressed pancreatic cancer. Results: We profiled miRNAs changes induced by Ole and identified miR-190b-5p as a novel functional player in Ole-mediated pancreatic cancer suppression. Further on, we reported that TCF4 in Wnt signaling was a direct target of miR-190b-5p. The suppression of Wnt signaling by miR-190b-5p was attributed to Ole-induced tumor inhibition in a pancreatic cancer model. Finally, we showed that miR-190b-5p was downregulated in human clinical cancer samples. Conclusion: In summary, we discovered that Ole carried anti-pancreatic cancer function. MiR-190b-5p induced by Ole was a potential therapeutic target.