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

Authors Li X, Li Y, Wan L, Chen R, Chen F

Received 15 December 2016

Accepted for publication 9 June 2017

Published 11 September 2017 Volume 2017:10 Pages 4455—4464

DOI https://doi.org/10.2147/OTT.S130378

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr Chiung-Kuei Huang

Xin Li,1 Yan Li,2 Li Wan,3 Rui Chen,4 Fei Chen5

1Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 2Department of Ophthalmology and Otorhinolaryngology, Lecong Hospital of Guangzhou Medical University, Foshan, 3Department of Laboratory Medicine, The Fourth Affiliated Hospital of Guangzhou Medical University, 4Key Laboratory for Major Obstetric Diseases in Guangdong Province, Key Laboratory of Reproduction and Genetics in Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, 5Department of Histology and Embryology, School of Basic Sciences, Guangzhou Medical University, Guangzhou, People’s Republic of China


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

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