MicroRNA-588 regulates invasion, migration and epithelial–mesenchymal transition via targeting EIF5A2 pathway in gastric cancer

Xiaorong Zhou,1 Manli Xu,2 Yonghong Guo,1 Ling Ye,1 Limin Long,1 Haiqin Wang,1 Pan Tan,1 Meili Xu1 1Department of Gerontology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; 2Department of Basic Medicine, Guizhou College of Health Professions, Tongren, Guizhou, 554300, China Background: miRNAs are potential regulators of genes in many cancers. Here, we confirmed that the expression of miR-588 decreased in gastric cancer (GC) tissues and cells.Materials and methods: Sixty-seven GC tissues along with noncancerous tissues adjacent to them were included in the study. Quantitative real-time reverse transcription-PCR study was done to quantify the expression levels of mature miRNA. The expression of proteins was determined by Western blot and transwell chamber assay for invasion and migration studies. Immunohistochemical analysis and luciferase assay were done for evaluating the expression of epithelial–mesenchymal transition (EMT) markers and activity of EIF5A2, respectively. In vivo metastatic assay was done by injecting MGC-803 cells into nude mice.Results: In the 5-year predicted survival study of GC patients included in the study, we found that miR-588 acted as a specific prognostic marker. Overexpression of miR-588 resulted in suppression of cell invasion, migration and progression of EMT, whereas suppression of miR-588 inverted the effects in both in vivo and in vitro experiments. miR-588 retained EIF5A2 by directly binding to the 3´-UTR. EIF5A2 was overexpressed in GC tissue samples, and the expression of miR-588 was inversely correlated to the levels of EIF5A2. The impact of miR-588 on invasion, migration and progression of EMT may be partially due to miR-588–mediated alterations of EiF5A2.Conclusion: Overall, the findings of the study suggest that miR-588 acts as a tumor suppressor by regulating the invasion, migration and EMT via EIF5A2 pathway, hence presenting miR-588 as a prognostic marker as well as a therapeutic target for GC. Keywords: miR-588, gastric cancer, EIF5A2, EMT