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Int. J. Mol. Sci. 2016, 17(10), 1633; doi:10.3390/ijms17101633

MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais

1
Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190 Gwangju, Korea
2
Biomolecular Function Research Branch Division of Precision Medicine and Cancer Informatics, Division of Precision Medicine and Cancer Informatics, National Cancer Center, 410-769 Goyang, Korea
3
Department of Biochemistry, Chonnam National University Medical School, 5 Hakdong, 501-190 Gwangju, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Martin Pichler
Received: 26 July 2016 / Revised: 1 September 2016 / Accepted: 12 September 2016 / Published: 27 September 2016
(This article belongs to the Collection Regulation by Non-Coding RNAs)
View Full-Text   |   Download PDF [10930 KB, uploaded 27 September 2016]   |  

Abstract

Emerging evidence supports a fundamental role for microRNAs (miRNA) in regulating cancer metastasis. Recently, microRNA-375 (miR-375) was reported to be downregulated in many types of cancers, including gastric cancer. Increase in the expression of Recepteur d’Origine Nantais (RON), a receptor tyrosine kinase, has been reported in tumors. However, the function of miR-375 and RON expression in gastric cancer metastasis has not been sufficiently studied. In silico analysis identified miR-375 binding sites in the 3′-untranslated regions (3′-UTR) of the RON-encoding gene. Expression of miR-375 resulted in reduced activity of a luciferase reporter containing the 3′-UTR fragments of RON-encoding mRNA, confirming that miR-375 directly targets the 3′-UTR of RON mRNA. Moreover, we found that overexpression of miR-375 inhibited mRNA and protein expression of RON, which was accompanied by the suppression of cell proliferation, migration, and invasion in gastric cancer AGS and MKN-28 cells. Ectopic miR-375 expression also induced G1 cell cycle arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of retinoblastoma (Rb). Knockdown of RON by RNAi, similar to miR-375 overexpression, suppressed tumorigenic properties and induced G1 arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of Rb. Thus, our study provides evidence that miR-375 acts as a suppressor of metastasis in gastric cancer by targeting RON, and might represent a new potential therapeutic target for gastric cancer. View Full-Text
Keywords: microRNA-375; Recepteur d’Origine Nantais; gastric cancer microRNA-375; Recepteur d’Origine Nantais; gastric cancer
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MDPI and ACS Style

Lian, S.; Park, J.S.; Xia, Y.; Nguyen, T.T.; Joo, Y.E.; Kim, K.K.; Kim, H.K.; Jung, Y.D. MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais. Int. J. Mol. Sci. 2016, 17, 1633.

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