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

Xiangguo Duan; Tao Zhang; Shuqin Ding; Jun Wei; Chunxia Su; Hongpeng Liu; Guangxian Xu

doi:10.1371/journal.pone.0138011

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

PLoS One. 2015 Sep 18;10(9):e0138011. doi: 10.1371/journal.pone.0138011. eCollection 2015.

Authors

Xiangguo Duan¹, Tao Zhang², Shuqin Ding³, Jun Wei⁴, Chunxia Su³, Hongpeng Liu³, Guangxian Xu¹

Affiliations

¹ School of LaboratoryMedicine, Ningxia Medical University, Yinchuan, 750004, China; General Hospital of Ningxia Medical University, Yinchuan, 750004, China; Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Yinchuan, 750004, China.
² School of LaboratoryMedicine, Ningxia Medical University, Yinchuan, 750004, China; Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Yinchuan, 750004, China; Taian City Central Hospital,Taian City, Shandong Province, 271000, China.
³ School of LaboratoryMedicine, Ningxia Medical University, Yinchuan, 750004, China; Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Yinchuan, 750004, China.
⁴ General Hospital of Ningxia Medical University, Yinchuan, 750004, China; Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Yinchuan, 750004, China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / genetics
Animals
Autophagy / genetics
Autophagy-Related Protein-1 Homolog
Gene Expression Regulation, Enzymologic
HEK293 Cells
Humans
Macrophages / metabolism*
Macrophages / microbiology*
Mice
MicroRNAs / physiology*
Mycobacterium bovis / growth & development*
Mycobacterium bovis / physiology
Phagosomes / genetics
Phagosomes / microbiology
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
RAW 264.7 Cells

Substances

3' Untranslated Regions
MicroRNAs
Mirn17 microRNA, mouse
Autophagy-Related Protein-1 Homolog
Protein Serine-Threonine Kinases
Ulk1 protein, mouse

Grants and funding

This work was funded by the National Natural Science Foundation of China (No. 31472168, 31160494), the program for New Century Excellent Talents in University (No. NCET 11-11023), and the 2013 Clinical Laboratory Diagnosis Creative Group Open Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.