Down regulation of miR-148a is related to enhanced pancreatic cancer pathogenesis through targeting GLUT1

Int J Clin Exp Pathol. 2018 Oct 1;11(10):4950-4956. eCollection 2018.

Abstract

Pancreatic cancer (PC) is an aggressive malignancy with one of the worst mortality rates in the world. Multiple factors, including a complex and poorly understood pathophysiology and difficulty in early detection and diagnosis make successful treatment of pancreatic cancer extremely challenging. In this study, we first detected the expressions of eight selected miRNAs which are predicted repress GLUT1 expression by targeting 3'UTR. We found miR-148a had a significantly down regulated expression and miR-148a level has an inverse correlation with the expression of GLUT1 in PC tissues. Subsequently, examined by dual-luciferase assay and western blot, we confirmed that miR-148a suppressed GLUT1 expression by directly targeting 3'UTR of GLUT1 mRNA. Finally, biological study in two pancreatic cancer cell lines indicates that miR-148a function as a tumor suppressor gene through repressing pancreatic cancer cell proliferation, migration and invasion. We first identified miR-148a, which has down regulated expression in pancreatic cancer tissues, plays as a cancer inhibitor through targeting GLUT1. This study sheds light on the roles of miRNAs in the pathogenesis of pancreatic cancer and may be helpful for clinical diagnosis and treatment.

Keywords: GLUT1; Pancreatic cancer; miRNA.