MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy

Liu, Feng; Chen, Jianxia; Wang, Peng; Li, Haohao; Zhou, Yunting; Liu, Haipeng; Z, Liu; Zheng, Ruijuan; Wang, Lin; Yang, Hua; Cui, Zhenling; Wang, Fei; Huang, Xiaochen; Wang, Jie; Wang, Sha; Xiao, He-Ping; Ge, Baoxue

doi:10.1038/s41467-018-06836-4

Cited by 106 publications

(75 citation statements)

References 64 publications

(78 reference statements)

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“…Induction of miR-27a was found to target the Ca2 transporter Cacna2d3 directly and downregulate ER Ca2 signaling to inhibit autophagy, thus promoting the intracellular survival of MTB. 129 lncRNA, PCED1B-AS1, modulates macrophage apoptosis and autophagy by targeting the miR-155 axis inactive TB. It may represent a novel early diagnostic marker of active TB and may be useful in the development of potential therapeutic interventions for patients with TB.…”

Section: Mirs Regulate Autophagy In Tuberculosismentioning

confidence: 99%

“…Calcium channel, voltage‐dependent, alpha‐2/delta subunit 3 (CACNA2D3) is an auxiliary member of the alpha‐2/delta subunit family of the voltage‐dependent calcium channel complex. Induction of miR‐27a was found to target the Ca2 transporter Cacna2d3 directly and downregulate ER Ca2 signaling to inhibit autophagy, thus promoting the intracellular survival of MTB …”

Section: Introductionmentioning

confidence: 99%

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MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

et al. 2019

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Autophagy is a highly conserved catabolic process and fundamental biological process in eukaryotic cells. It recycles intracellular components to provide nutrients during starvation and maintains quality control of organelles and proteins. In addition, autophagy is a well‐organized homeostatic cellular process that is responsible for the removal of damaged organelles and intracellular pathogens. Moreover, it also modulates the innate and adaptive immune systems. Micro ribonucleic acids (microRNAs) are a mature class of post‐transcriptional modulators that are widely expressed in tissues and organs. And, it can suppress gene expression by targeting messenger RNAs for translational repression or, at a lesser extent, degradation. Research indicates that microRNAs regulate autophagy through different pathways, playing an essential role in the treatment of various diseases. It is an important regulator of fundamental cellular processes such as proliferation, autophagy, and cell apoptosis. In this review article, we first review the current knowledge of autophagy and the function of microRNAs. Then, we summarize the mechanism of autophagy and the signaling pathways related to autophagy by citing at least the main proteins involved in the different phases of the process. Second, we introduce other members of RNA and report some examples in various pathologies. Finally, we review the current literature regarding microRNA‐based therapies for cancer, atherosclerosis, cardiac disease, tuberculosis, and viral diseases. MicroRNAs can cause autophagy upregulation or downregulation by targeting genes or affecting autophagy‐related signaling pathways. Therefore, the microRNAs have a huge potential in autophagy regulation, and it is the function as diagnostic and prognostic markers.

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Section: Mirs Regulate Autophagy In Tuberculosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

et al. 2019

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“…For example, among miRNAs that are upregulated in TB patients, miR-146a-5p, miR-21-5p, miR-99b-5p and miR-132-5p negatively regulate host inflammatory pathways triggered by Toll-like receptor (TLR) signaling in myeloid cells, thus promoting M. tuberculosis survival [ 21 ]. Other miRNAs that are upregulated in M. tuberculosis -infected macrophages, like miR-27a-5p, miR-33, miR-125-5p and miR-144-5p, inhibit autophagosome formation and M. tuberculosis killing by macrophages [ 22 , 23 ]. MiR-29a-3p and miR-125-5p, both upregulated in infected macrophages, directly target IFNγ and TNFα, hence suppressing the immune response to intracellular M. tuberculosis [ 24 , 25 ].…”

Section: Micrornas In Tuberculosis Pathogenesismentioning

confidence: 99%

“…MiR-223-3p, which plays a relevant role in myeloid cells biology and is enriched in neutrophils and macrophages [ 53 ], is abundantly expressed in blood and lung parenchyma in human and murine TB [ 54 , 55 , 56 ]. In myeloid cells, miR-223-3p controls NF-κB activity and negatively regulates cytokine release in TB [ 22 , 54 ]. Direct targets of miR-223-3p are represented by the chemokine C-X-C motif ligand 2 (CXCL2), C-C motif ligand 3 (CCL3), and IL-6 [ 54 ].…”

Section: Suppression Of Inflammatory Signaling Pathwaysmentioning

confidence: 99%

Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers

Sinigaglia

Peta

Riccetti

et al. 2020

Cells

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Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the most lethal infectious diseases with estimates of approximately 1.4 million human deaths in 2018. M. tuberculosis has a well-established ability to circumvent the host immune system to ensure its intracellular survival and persistence in the host. Mechanisms include subversion of expression of key microRNAs (miRNAs) involved in the regulation of host innate and adaptive immune response against M. tuberculosis. Several studies have reported differential expression of miRNAs during active TB and latent tuberculosis infection (LTBI), suggesting their potential use as biomarkers of disease progression and response to anti-TB therapy. This review focused on the miRNAs involved in TB pathogenesis and on the mechanism through which miRNAs induced during TB modulate cell antimicrobial responses. An attentive study of the recent literature identifies a group of miRNAs, which are differentially expressed in active TB vs. LTBI or vs. treated TB and can be proposed as candidate biomarkers.

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“…According to previous reports, at least 30 miRNAs may be involved in M. tb infection, and at least 10 of these might be associated with the survival of M. tb in macrophages. MiR-27a expression was up-regulated, and expression of its target protein, CACNA2D3, an ER-located Ca 2+ transporter, was reduced during M. tb infection leading to inhibition of autophagosome formation (Liu et al, 2018). The miR-33 locus was induced by M. tb infection to reprogram autophagy and host lipid metabolism and enable M. tb to survive intracellularly and persist in the hosts (Ouimet et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of miR-378d Increased Rab10 Expression to Help Clearance of Mycobacterium tuberculosis in Macrophages

Zhu

Xiao

Delai

et al. 2020

Front. Cell. Infect. Microbiol.

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Mycobacterium tuberculosis (M. tb) can survive in the hostile microenvironment of cells by escaping host surveillance, but the molecular mechanisms are far from being fully understood. MicroRNAs might be involved in regulation of this intracellular process. By RNAseq of M. tb-infected PMA-differentiated THP-1 macrophages, we previously discovered down-regulation of miR-378d during M. tb infection. This study aimed to investigate the roles of miR-378d in M. tb infection of THP-1 cells by using a miR-378d mimic and inhibitor. First, M. tb infection was confirmed to decrease miR-378d expression in THP-1 and Raw 264.7 macrophages. Then, it was demonstrated that miR-378d mimic promoted, while its inhibitor decreased, M. tb survival in THP-1 cells. Further, the miR-378d mimic suppressed, while its inhibitor enhanced the protein production of IL-1β, TNF-α, IL-6, and Rab10 expression. By using siRNA of Rab10 (siRab10) to knock-down the Rab10 gene in THP-1 with or without miR-378d inhibitor transfection, Rab10 was determined to be a miR-378d target during M. tb infection. In addition, a dual luciferase reporter assay with the Rab10 wild-type sequence and mutant for miR-378d binding sites confirmed Rab10 as the target of miR-378d associated with M. tb infection. The involvement of four signal pathways NF-κB, P38, JNK, and ERK in miR-378d regulation was determined by detecting the effect of their respective inhibitors on miR-378d expression, and miR-378d inhibitor on activation of these four signal pathways. As a result, activation of the NF-κB signaling pathway was associated with the down-regulation of miR-378d. In conclusion, during M. tb infection of macrophages, miR-378d was down-regulated and functioned on decreasing M. tb intracellular survival by targeting Rab10 and the process was regulated by activation of the NF-κB and induction of pro-inflammatory cytokines IL-1β, TNF-α, IL-6. These findings shed light on further understanding the defense mechanisms in macrophages against M. tb infection.

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MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy

Cited by 106 publications

References 64 publications

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers

Down-Regulation of miR-378d Increased Rab10 Expression to Help Clearance of Mycobacterium tuberculosis in Macrophages

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