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- Title
MicroRNA 17-5p regulates autophagy in Mycobacterium tuberculosis-infected macrophages by targeting Mcl-1 and STAT3.
- Authors
Kumar, Ranjeet; Sahu, Sanjaya Kumar; Kumar, Manish; Jana, Kuladip; Gupta, Pushpa; Gupta, Umesh D.; Kundu, Manikuntala; Basu, Joyoti
- Abstract
Autophagy plays a crucial role in the control of bacterial burden during Mycobacterium tuberculosis infection. MicroRNAs (miRNAs) are small non-coding RNAs that regulate immune signalling and inflammation in response to challenge by pathogens. Appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the role of miRNAs in regulating M. tuberculosis-induced autophagy in macrophages. Here, we demonstrate that M. tuberculosis infection leads to downregulation of miR-17 and concomitant upregulation of its targets Mcl-1 and STAT3, a transcriptional activator of Mcl-1. Forced expression of miR-17 reduces expression of Mcl-1 and STAT3 and also the interaction between Mcl-1 and Beclin-1. This is directly linked to enhanced autophagy, because Mcl-1 overexpression attenuates the effects of miR-17. At the same time, transfection with a kinase-inactive mutant of protein kinase C δ (PKCδ) (an activator of STAT3) augments M. tuberculosis-induced autophagy, and miR-17 overexpression diminishes phosphorylation of PKCδ, suggesting that an miR-17/PKC δ/STAT3 axis regulates autophagy during M. tuberculosis infection.
- Subjects
MICRORNA; AUTOPHAGY; MYCOBACTERIUM tuberculosis; MACROPHAGES; CELLULAR signal transduction
- Publication
Cellular Microbiology, 2016, Vol 18, Issue 5, p679
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/cmi.12540