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.

Keywords:

• miR-509-5p
• pancreatic cancer
• MDM2
• proliferation
• migration
• invasion

Supplementary material

Figure S1 Real-time quantitative polymerase chain reaction was performed to examine the expression of miR-509-5p in the isolated islet cells from pancreas (n=3) and three pancreatic cancer cell lines.

Notes: Results are expressed relative to the control value. *P<0.05 vs islet cells.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (31401240, 81202604), Guangdong Natural Science Foundation (2015A030310153), Guangdong Medical Research Foundation (B2014185, B2014190), and Guangzhou Medical University Science Foundation (2013C01).

Disclosure

The authors report no conflicts of interest in this work.