MiR-424-5p Promotes Cell Invasion And Migration By Targeting CYLD In Human Pancreatic Cancer

Purpose: The aim of the present study is to detect the expression level of miR-424-5p and CYLD in pancreatic cancer tissues,and to explore the effect of miR-424-5p on the invasion and migration of human pancreatic cancer cells and uncover the underlying mechanism.Methods: Investigated the expression of miR-424-5p and CYLD in 12 pancreatic cancer and adjacent non-cancer tissues by Quantitative real-time PCR(qRT-PCR). These tissues were collected from patients who were diagnosed and received surgery from January 2014 to January 2015 in Department of hepatobiliary surgery of General Hospital of PLA Second Artillery. miR-424-5p mimics/inhibitors and their negative controls were transfected into PANC-1 cells by use of lipofectamine 2000, following by transwell and wound healing assays, which were used for investigating the capacity of cell invasion and migration. Meanwhile, protein levels of CYLD and E-cadherin were examined through western blotting. Luciferase reporter assay was used to validate CYLD as a target of mi R-424-5p.Results: qRT-PCR analysis showed that the levels of miR-424-5p expression in pancreatic cancer were significantly higher than in the adjacent non-cancer tissues. The levels of CYLD mRNA expression in pancreatic cancer were lower than in the adjacent non-cancer tissues. The inverse correlation of miR-424-5p and CYLD expression levels were examined by Pearson correlation analysis(R=-0.811,P<0.01). qRT-PCR analysis showed that miR-424-5p decreased and increased by transfected the miR-424-5p inhibitors and mimics respectively. miR-424-5p mimics promoted migratory ability and invasive capacity of PANC-1 cells 24~48h after transfection compared with negative control. On the contrary, miR-424-5p inhibitors reduced migratory ability and invasive capacity of PANC-1 cells.Bioinformatics and dual-luciferase reportor assay demonstrated that CYLD is a target of miR-424-5p in PANC-1. Meanwhile, western blotting showed that mi R-424-5p mimics inhibited CYLD and E-cadherin protein expression.Conclusions: The levels of mi R-424-5p expression in the pancreatic cancer tissues were higher than in the adjacent non-cancer tissues, whereas the levels of CYLD expression in the pancreatic cancer tissues were lower than in the adjacent non-cancer tissues. miR-424-5p may increase pancreatic cancer cells invasion and migration by targeting CYLD, and thus potentially serving as a new therapeutic target for pancreatic cancer.