MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais
AbstractEmerging 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
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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.
Lian S, Park JS, Xia Y, Nguyen TT, Joo YE, Kim KK, Kim HK, Jung YD. MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais. International Journal of Molecular Sciences. 2016; 17(10):1633.Chicago/Turabian Style
Lian, Sen; Park, Jung S.; Xia, Yong; Nguyen, Thi T.; Joo, Young E.; Kim, Kyung K.; Kim, Hark K.; Jung, Young D. 2016. "MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais." Int. J. Mol. Sci. 17, no. 10: 1633.
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