Open AccessMicroRNA 17‐5p regulates autophagy in Mycobacterium tuberculosis ‐infected macrophages by targeting Mcl‐1 and STAT3
Author(s) -
Kumar Ranjeet,
Sahu Sanjaya Kumar,
Kumar Manish,
Jana Kuladip,
Gupta Pushpa,
Gupta Umesh D.,
Kundu Manikuntala,
Basu Joyoti
Publication year - 2016
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12540
Subject(s) - autophagy , biology , mycobacterium tuberculosis , stat3 , downregulation and upregulation , microrna , phagosome , microbiology and biotechnology , tuberculosis , kinase , activator (genetics) , cancer research , phosphorylation , phagocytosis , apoptosis , medicine , gene , genetics , pathology
Summary 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.