Abstract
Pancreatic cancer (PC) is one of the most aggressive malignancies worldwide. MicroRNAs play an important role in the development and progression of PC, but little is known about the role of miR-204 in PC. In this study, we revealed that miR-204 was downregulated in PC tissues and cell lines, and its expression was closely correlated with aggressive clinicopathological features of PC patients. Both gain- and loss-of-function studies showed that miR-204 overexpression inhibits the proliferation, migration and invasion of PC cells, whereas miR-204 knockdown had the opposite effects. Using mouse models, we found that miR-204 overexpression suppressed PC tumor growth in vivo. Moreover, miR-204 overexpression notably suppressed epithelial-mesenchymal transition (EMT) of PC cells, and through bioinformatics analysis and dual-luciferase reporter assay, ZEB1, a critical EMT promoter, was identified to be the functional target of miR-204 in PC cells. Rescue experiments further showed that ZEB1 overexpression abrogated the effects of miR-204 in PC cells. Collectively, these findings demonstrated the tumor suppressive role of miR-204 in PC through the ZEB1/EMT axis, therefore providing a novel therapeutic target for human PC.