microRNA-17-5p Modulates Bacille Calmette-Guerin Growth in RAW264.7 Cells by Targeting ULK1

• Published in: PloS one 2015-09, Vol.10 (9), p.e0138011-e0138011
• Main Authors: Duan, Xiangguo, Zhang, Tao, Ding, Shuqin, Wei, Jun, Su, Chunxia, Liu, Hongpeng, Xu, Guangxian
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Acidification; Animals; Apoptosis; Autophagy; Autophagy - genetics; Autophagy-Related Protein-1 Homolog; Bacillus Calmette-Guerin vaccine; BCG; Cell death; Cell survival; Gene Expression Regulation, Enzymologic; Genes; HEK293 Cells; Hospitals; Humans; Immune response; Immunology; Infections; Intracellular; Kinases; Laboratories; Macrophages; Macrophages - metabolism; Macrophages - microbiology; Mice; MicroRNA; MicroRNAs; MicroRNAs - physiology; miRNA; Mycobacterium bovis; Mycobacterium bovis - growth & development; Mycobacterium bovis - physiology; Mycobacterium tuberculosis; Phagocytosis; Phagosomes; Phagosomes - genetics; Phagosomes - microbiology; Protein kinases; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; RAW 264.7 Cells; Ribonucleic acid; RNA; Target recognition; Tuberculosis; Veterinary medicine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138011

To explore the potential roles of miRNAs in controlling the survival of mycobacteria in macrophages, miR-17-5p in the regulation of Bacillus Calmette-Guérin(BCG)growth in the macrophage RAW264.7 cells was interrogated. Our results reveal that an infection of BCG shows a time-dependent up-regulation of miR-17-5p in RAW264.7 cells in early phase; importantly, excessive expression of miR-17-5p in these cells exhibits an increased propagation of intracellular BCG. Mechanistically, the Unc-51 like autophagy activating kinase 1 (ULK1), an initial molecular of autophagy are identified as novel target of miR-17-5p, the miR-17-5p is capable of targeting down-regulating the expression of ULK1 protein. In addition, an overexpression of miR-17-5p in RAW264.7 cells is correlated with repression of ULK1 and the autophagosome related proteins LC3I/II. These results imply that miR-17-5p may be able to arrest the maturation of mycobacterial phagosomes in part by targeting ULK1, subsequently reduces the ability of host cells to kill intracellular BCG.