MiR-9-5p inhibits pancreatic cancer cell proliferation, invasion and glutamine metabolism by targeting GOT1

Abstract

MicroRNAs (miRNAs) play crucial roles in the pancreatic carcinogenesis and progression. In the present study, we found that miR-9-5p was significantly downregulated in pancreatic cancer tissues and cell lines. The expression levels of miR-9-5p were negatively correlated with tumor stage and vessel invasion. Log-rank tests demonstrated that low expression of miR-9-5p was strongly correlated with poor overall survival in pancreatic cancer patients. Moreover, overexpression of miR-9-5p remarkably inhibited pancreatic cancer cell proliferation by enhancing cell apoptosis and significantly suppressed the invasion of pancreatic cancer cells, whereas low expression of miR-9-5p exhibited the opposite effect. Bioinformatics analysis revealed that GOT1 was a potential target of miR-9-5p, and miR-9-5p inhibited the expression level of GOT1 mRNA by direct binding to its 3′-untranslated region (3′UTR). Expression of miR-9-5p was negatively correlated with GOT1 in pancreatic cancer tissues. Moreover, modulation of miR-9-5p expression could affect the glutamine metabolism and redox homeostasis in pancreatic cancer cells. Furthermore, downregulation of GOT1 counteracted the effects of miR-9-5p repression, whereas its overexpression reversed tumor inhibitory effects of miR-9-5p. Collectively, this study suggested that miR-9-5p regulates GOT1 expression in pancreatic cancer, thereby stunting proliferation, invasion, glutamine metabolism and redox homeostasis, and that miR-9-5p may serve as a prognostic or therapeutic target for pancreatic cancer.