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Effect and related mechanism of microRNA-520a up-regulation on malignant biological behaviors and enhanced radiosensitivity in gastric cancer cells

YANG Hui;LI Xiang-yong;Department of Hematology and Oncology Ward 2, the 904 Hospital of the Joint Logistics Support Force of the Chinese People′s Liberation Army;  
Objective To explore the effect and related mechanisms of microRNA-520 a(miR-520 a) up-regulation on malignant biological behaviors and enhanced radiosensitivity in gastric cancer cells. Methods Gastric cancer MGC-803 cells were divided into blank group, up-regulation group and down-regulation group. The blank group was added with conventional cell culture medium, the down-regulation group was transfected with p-Genesil, and the up-regulation group was transfected with p-Genesil-miR-520 a. The conditions of cell transfection were checked in each group; besides, the abilities of cell proliferation, apoptosis, migration, and invasion, as well as the protein expression of Janus kinase 3(JAK3)/signal transducer and activator of transcription 3(STAT3) signaling pathway, were detected in each group. After the end of the transfection, cells in each group received an X-ray irradiation at certain doses, and the status of cell colony forming was observed; in addition, the mean fatality dose(D0), cell survival fraction under the X-ray irradiation at a dose of 2 Gy(SF2) and radiosensitivity enhancement ratio(SER) were calculated. Results After 48 hours of the transfection, the up-regulation group exhibited higher miR-520 a expression than the blank group, and the down-regulation group exhibited lower miR-520 a expression than the blank and up-regulation groups(all P0.05). Twenty-four, 48 and 72 hours after the stable transfection, the up-regulation group reported lower rates of cell proliferation than the blank and down-regulation groups, and the down-regulation group reported higher rates of cell proliferation than the blank group; after 72 hours, the up-regulation and down-regulation groups exhibited higher apoptosis rates than the blank group, in terms of which the up-regulation group was higher than the down-regulation group(all P0.05). The numbers of cell migration and invasion were fewer in the up-regulation group than in the blank and down-regulation groups, but the numbers of cell migration and invasion in the down-regulation group were more than those in the blank group(all P0.05). The up-regulation group had increased SF2 value, D0 value and SER than the blank and down-regulation groups, and the down-regulation group had decreased SF2 value, D0 value and SER than the blank group(all P0.05). The expression of JAK3, STAT3, phosphorylated JAK3, and phosphorylated STAT3 proteins was lower in the up-regulation group than in the blank and down-regulation groups, and the expression of JAK3, STAT3, phosphorylated JAK3, and phosphorylated STAT3 proteins was higher in the down-regulation group than in the blank group(all P0.05). Conclusion Up-regulation of miR-520 a expression level can inhibit the proliferation, migration, and invasion of gastric cancer cells, promote apoptosis, and increase the enhanced radiosensitivity of the cells, which may play its role by affecting the expression of the JAK3/STAT3 signaling pathway.
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