MiR-509-5p inhibits cellular proliferation and migration via targeting MDM2 in pancreatic cancer cells

Abstract

Objective: This study aimed to explore the effect of miR-509-5p on pancreatic cancer progression and clarify the underlying mechanisms. Methods: Real-time quantitative reverse transcription polymerase chain reaction was employed to determine miR-509-5p expression in pancreatic cancer tissues and noncancerous adjacent tissues. CCK-8 and Transwell experiments were employed to examine cellular proliferation, migration, and invasion after miR-509-5p mimic or inhibitor transfection. Bioinformatics tools were used to identify the target gene of miR-509-5p, and cotransfection of the target gene and miR-509-5p mimic was performed to determine the effect on the proliferation and migration of pancreatic cancer cells. A xenograft mouse model and histological analysis were also used to test the effect of miR-509-5p on tumor growth in vivo. Results: miR-509-5p expression was dramatically downregulated in pancreatic cancer tissues and in pancreatic cancer cell lines. miR-509-5p mimic markedly inhibited PANC-1 cell proliferation, migration, and invasion. Conversely, miR-509-5p inhibitor promoted PANC-1 cell proliferation, migration, and invasion. Furthermore, the 3′UTR–specific target site luciferase reporter assay also showed that miR-509-5p negatively regulated MDM2 at the post-transcriptional level. miR-509-5p effectively reversed the MDM2 overexpression-induced increase in PANC-1 cell proliferation and invasion. Moreover, miR-509-5p inhibited tumor growth and accelerated cell death in the tumor samples. Conclusions: Our results suggested that miR-509-5p served as a new tumor suppressor via targeting the MDM2 gene, inhibiting pancreatic cancer progression.