Over-expression of microRNA-940 promotes cell proliferation by targeting GSK3β and sFRP1 in human pancreatic carcinoma

Increasing study reports that Wnt/beta-catenin signaling pathway plays an essential role in numerous cancers growth, progression and metastasis. Aberrant miR-940 expression has been studied in gastric and breast cancer. However, the molecular mechanism of miR-940 enhancing proliferation and metastatic ability in human pancreatic carcinoma is far from to know. Real-time PCR was used to quantify miR-940 expression. Luciferase reporter assays here were performed to verify the activity of Wnt/beta-catenin signaling pathway and targeting gene relationships, and immunofluorescence assay was applied to observe beta-catenin expressed intensity. Bioinformatics analysis together with in vivo and vitro functional analysis indicated the potential targeting genes of miR-940. Specimens from 15 pairs of patients with human pancreatic carcinoma were involoved to confirm the relationship between miR-940 expression and the GSK3 beta/sFRP1 through real-time PCR and western blot assays. Bioinformatics combined with cell luciferase function researches determined the possible regulation of miR-940 on the 3'-UTR of the GSK3 beta and sFRP1 genes, resulting in the Wnt/beta-catenin signaling activation. Further, miR-940 knockdown significantly recovered GSK3 beta and sFRP1 expression and relieved Wnt/beta-catenin-mediated cell invasion, migration, metastasis and proliferation. The ectopic up-regulation of miR-940 significantly suppressed GSK3 beta/sFRP1 expression and promoted pancreatic carcinoma proliferation and invasion. Our study suggested mechanistic relationship between miR-940 and Wnt/beta-catenin in the development and progression of pancreatic carcinoma through regulation of GSK3 beta and sFRP1. (C) 2016 Published by Elsevier Masson SAS.