MicroRNA-448 suppresses metastasis of pancreatic ductal adenocarcinoma through targeting JAK1/STAT3 pathway

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of malignant pancreatic tumor. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in tumorigenesis and progression of PDAC. In the present study, we demonstrated that miR-448 expression was downregulated in PDAC tissues and cell lines. Clinical association analysis indicated that low expression of miR-448 was associated with poor prognostic features and conferred a significant reduced survival of PDAC patients. Overexpression of miR-448 suppressed PDAC cell migration and invasion, while its loss showed the opposite effects on these cellular processes. In vivo experiments revealed that miR-488 restoration prohibited liver metastasis of PDAC in nude mice. Moreover, we found that Janus kinase 1 (JAK1) was a direct target gene of miR-448 in PDAC cells. We further demonstrated that the expression of JAK1 mRNA was upregulated in PDAC tissues. Notably, the expression of JAK1 mRNA was inversely correlated with the level of miR-448 in PDAC tissues. In addition, JAK1 knockdown showed similar effects of miR-448 on the metastasis of PDAC cells. JAK1/STAT3 pathway may be involved in the function of miR-448 in PDAC cells. Taken together, these findings suggest that miR-448 functions as a tumor suppressor in the development of PDAC through targeting the JAK1/STAT3 pathway.