MicroRNA-628-5p inhibits invasion and migration of human pancreatic ductal adenocarcinoma via suppression of the AKT/NF-kappa B pathway.

Abstract

The biological function and underlying mechanism of microRNA-628-5p (miR-628-5p) remains to be clarified in the growth and progression of pancreatic ductal adenocarcinoma (PDAC). Here, the expression levels of miR-628-5p in PDAC tissues and cells were detected by quantitative reverse transcriptase polymerase chain reaction and in situ hybridization. The relationship between miR-628-5p expression and clinicopathologic characteristics was examined in human PDAC tissue samples. Gain- and loss-of-function and the putative targets of miR-628-5p were evaluated in PDAC cell lines. The upstream and downstream signals of miR-628-5p in PDAC were also examined. MiR-628-5p was lowly expressed in PDAC tissues and cell lines, and low miR-628-5p expression in PDAC tissues was associated with poor clinicopathological characteristics and shorter overall survival. Functionally, restoration of miR-628-5p expression decreased PDAC cell proliferation, migration, invasion, and promoted cell apoptosis, whereas miR-628-5p silencing abolished these biological behaviors. MiR-628-5p was found to target and negatively regulate phospholipid scramblase 1 and insulin receptor substrate 1 expression, which resulted in the inhibition of the AKT/NF-κB signaling pathway. MYC knockdown led to miR-628-5p upregulation, whereas MYC overexpression repressed miR-628-5p expression. These findings indicate that miR-628-5p functions as a tumor-suppressive microRNA in PDAC and implicate miR-628-5p as a potential therapeutic target for PDAC patients.