MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9 

Abstract

Background: MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PAC). The expression level and role of miR-1252-5p in PAC remain unclear. Methods: qRT-PCR and in situ hybridization were used to detect miR-1252-5p expression in PAC cells and tissues. Associations between miR-1252-5p expression and clinical characteristics or overall survival (OS) were assessed based on 102 patients with PAC who underwent surgical resection. Gain and loss of function of miR-1252-5p was studied in the PAC cell lines, Panc-1 and BxPC 3 in vitro and in vivo. The direct targets of miR-1252-5p were analyzed using public databases and a dual-luciferase reporter assay.Results: The expression levels of miR-1252-5p are downregulated in PAC cell lines and tissue samples compared to control, and its expression is negatively associated with adverse clinical features and poor prognosis. In vitro and in vivo experiments show that miR-1252-5p overexpression inhibits the proliferation, migration, invasion and epithelial-mesenchymal transition of PAC cells, whereas miR-1252-5p knockdown enhances these biological behaviors. In addition, miR-1252-5p negatively regulates neural precursor cell expressed, developmentally downregulated 9 (NEDD9) by directly binding its 3'-UTR. NEDD9 restoration at least partially abolishes this effect of miR-1252-5p in PAC cells. Further mechanistic study revealed that the SRC/STAT3 pathway is involved in miR-1252-5p/NEDD9 mediation of biological behaviors in PAC. We also verified that Myb inhibited miR-1252-5p by directly binding at its promoter.Conclusion: MiR-1252-5p may act as a tumor-suppressing miRNA in PAC and may be a potential therapeutic target for PAC patients.