miR-203 suppresses pancreatic cancer cell proliferation and migration by modulating DUSP5 expression.

ABSTRACT

BACKGROUND: Pancreatic cancer (PC) is an insidious cancer that is commonly diagnosed in advanced stages. Therefore, it is necessary to understand PC-related mechanisms in order to discover new and reliable diagnostic biomarkers. It is known that miRNAs play a crucial role in carcinogenesis by targeting mRNAs. In this study we aimed to explore interaction between downregulated miR-203 and its upregulated target DUSP5 in PC. METHODS: Using bioinformatics approaches we identified the DUSP5 as a direct target gene of miR-203 and detected potential binding sites between miR-203 and DUSP5. Additionally, we evaluated subcellular location, expression level and prognostic value of DUSP5 in PC through using various bioinformatics tools. To investigate the relationship between miR-203 and DUSP5, we increased the expression levels of miR-203 by transfecting miR-203 mimics into the pancreatic cancer cell line, PANC-1. Finally, MTT, wound healing, and colony formation assays were performed to determine effect of overexpressed miR-203 on proliferation and migration of PANC-1 cells. RESULTS: We found that expression level of DUSP5 in pancreas tissue was one of the lowest tissue expression among all normal human tissue types. In addition, DUSP5 expression was upregulated both PC tissues and cell line and associated with poor overall survival in PC. Overexpression of miR-203 significantly downregulated expression level of DUSP5 and remarkably suppressed proliferation, migration and colony formation ability of PANC-1 cells. CONCLUSIONS: These findings suggest that miR-203 restrains proliferation and migration of PC cells by regulating oncogenic activity of DUSP5 in PC, thereby could be novel candidate biomarkers for PC diagnosis and treatment.