Summary: | 博士 === 國立臺灣大學 === 醫學檢驗暨生物技術學研究所 === 105 === Many bacterial pathogens can interfere with the cell cycle of infected cells to promotes their colonization. Bacterial pathogens also can interfere with the expression of microRNA(miRNA) in order to overcome host defenses. Salmonella enterica serovar Typhimurium promote G1/S transition and induce G2/M arrest to increase intracellular bacterial replication. We find that intracellular Salmonella induces the G2/M phase arrest of epithelial cells after 8 hours post-infection (h.p.i.), and it is dependent on the Salmonella-induced miR-376a. Inhibition of miR-376a in HT-29 cells results in decrease in intracellular replication of Salmonella at 16 and 24 h.p.i. Analysis of miR-376a targets reveals that the expression of two genes, ANGEL2 and PPP1R10, is inhibited by miR-376a. Inhibition of miR-376a reduces Salmonella-induced G2/M phase arrest, and silencing of ANGEL2 or PPP1R10 can reverse the inhibitory effect of the miR-376a antagomiR on G2/M phase arrest. Collectively, these findings suggest that upregulation of miR-376a upon Salmonella infection induces G2/M phase arrest by miR-376a targets inhibition.
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