MiR‐21‐5p regulates mycobacterial survival and inflammatory responses by targeting Bcl‐2 and TLR4 in <i>Mycobacterium tuberculosis</i>‐infected macrophages

Zhao, Zhonghua; Hao, Jinzhu; Li, Xia; Chen, Yanfang; Qi, Xiaoyan

doi:10.1002/1873-3468.13438

Cited by 39 publications

(21 citation statements)

References 21 publications

(28 reference statements)

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“…The same was observed in RAW264.7 and THP-1 cells where miR-21 enhanced M. tuberculosis survival and apoptosis and attenuated the secretion of inflammatory cytokines (IL-1␤, IL-6, and TNF-␣) by targeting B-cell lymphoma-2 (Bcl-2) and Toll-like receptor 4 (TLR4) (Fig. 4A) (107). Finally, miR-21 levels also increased in PPD-MPT64-stimulated RAW264.7 cells in contrast to PPD-stimulated cells, showing that M. tuberculosis immunogenic protein MPT64 upregulates miR-21 due to increased NF-B expression, leading to the upregulation of Bcl-2, an antiapoptotic protein, thus decreasing cell death (Fig.…”

Section: Role Of Validated Mirna In Different Stages Of Diseasesupporting

confidence: 66%

Unraveling the Role of MicroRNAs in Mycobacterium tuberculosis Infection and Disease: Advances and Pitfalls

2020

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Tuberculosis (TB) is an infectious disease of extremely high epidemiological burden worldwide that is easily acquired through the inhalation of infected respiratory droplets. The complex pathogenesis of this infection spans from subjects never developing this disease despite intense exposure, to others in which immune containment fails catastrophically and severe or disseminated forms of disease ensue. In recent decades, microRNAs (miRNAs) have gained increasing attention due to their role as gene silencers and because of their altered expression in diverse human diseases, including some infections. Recent research regarding miRNAs and TB has revealed that the expression profile for particular miRNAs clearly changes upon Mycobacterium tuberculosis infection and also varies in the different stages of this disease. However, despite the growing number of studies—some of which have even proposed some miRNAs as potential biomarkers—methodological variations and key differences in relevant factors, such as sex and age, cell type analyzed, M. tuberculosis strain, and antimicrobial therapy status, strongly hinder the comparison of data. In this review, we summarize and discuss the literature and highlight the role of selected miRNAs that have specifically and more consistently been associated with M. tuberculosis infection, together with a discussion of the possible gene and immune regulation pathways involved.

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Section: Role Of Validated Mirna In Different Stages Of Diseasesupporting

confidence: 66%

Unraveling the Role of MicroRNAs in Mycobacterium tuberculosis Infection and Disease: Advances and Pitfalls

2020

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“…Thus, the non-coding regulators igniting and propagating COVID-19 may provide potential mechanistic explanations to the hazards incurred by at-risk populations, and our findings bring ncRNAs at large, and DANCR and NEAT1 in particular, to the realm of COVID-19 and its aftermath. Further suggestive of the inter-individual risk disparity in COVID-19 is the observed differential expression by sex of several miRs including miR-21-5p, which has been previously observed to be dysregulated and associated with immune function in infectious scenarios ( 151 – 154 ). In the current study, we also noted sex-related changes in the activity of cholinergic and inflammatory elements, inversely correlated to DANCR’s expression levels.…”

Section: Discussionmentioning

confidence: 76%

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

2020

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The COVID-19 pandemic exerts inflammation-related parasympathetic complications and post-infection manifestations with major inter-individual variability. To seek the corresponding transcriptomic origins for the impact of COVID-19 infection and its aftermath consequences, we sought the relevance of long and short non-coding RNAs (ncRNAs) for susceptibility to COVID-19 infection. We selected inflammation-prone men and women of diverse ages among the cohort of Genome Tissue expression (GTEx) by mining RNA-seq datasets from their lung, and blood tissues, followed by quantitative qRT-PCR, bioinformatics-based network analyses and thorough statistics compared to brain cell culture and infection tests with COVID-19 and H1N1 viruses. In lung tissues from 57 inflammation-prone, but not other GTEx donors, we discovered sharp declines of the lung pathology-associated ncRNA DANCR and the nuclear paraspeckles forming neuroprotective ncRNA NEAT1. Accompanying increases in the acetylcholine-regulating transcripts capable of controlling inflammation co-appeared in SARS-CoV-2 infected but not H1N1 influenza infected lung cells. The lung cells-characteristic DANCR and NEAT1 association with inflammation-controlling transcripts could not be observed in blood cells, weakened with age and presented sex-dependent links in GTEx lung RNA-seq dataset. Supporting active involvement in the inflammatory risks accompanying COVID-19, DANCR’s decline associated with decrease of the COVID-19-related cellular transcript ACE2 and with sex-related increases in coding transcripts potentiating acetylcholine signaling. Furthermore, transcription factors (TFs) in lung, brain and cultured infected cells created networks with the candidate transcripts, indicating tissue-specific expression patterns. Supporting links of post-infection inflammatory and cognitive damages with cholinergic mal-functioning, man and woman-originated cultured cholinergic neurons presented differentiation-related increases of DANCR and NEAT1 targeting microRNAs. Briefly, changes in ncRNAs and TFs from inflammation-prone human lung tissues, SARS-CoV-2-infected lung cells and man and woman-derived differentiated cholinergic neurons reflected the inflammatory pathobiology related to COVID-19. By shifting ncRNA differences into comparative diagnostic and therapeutic profiles, our RNA-sequencing based Resource can identify ncRNA regulating candidates for COVID-19 and its associated immediate and predicted long-term inflammation and neurological complications, and sex-related therapeutics thereof. Our findings encourage diagnostics of involved tissue, and further investigation of NEAT1-inducing statins and anti-cholinergic medications in the COVID-19 context.

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“…These studies showed that certain miRNAs are significantly upregulated or down-regulated in inflammation or apoptosis-related diseases, which are concomitant with increased levels of inflammatory cytokines, including IL-1b, IL-6 and TNF-a. 11 Using a LPS-induced mice lung injury model, Cai et al found that miR-214 and miR-451 were significantly up-regulated, while miR-16, miR-23a, miR-24 and miR-199a were obviously down-regulated. In addition, they found miR-16 was involved in regulation of posttranscription of IL-6 and TNF-a in LPS-stimulated A549 cells.…”

Section: Discussionmentioning

confidence: 99%

“…19 Zhao et al demonstrated that miR-21 regulated mycobacterial survival and inflammatory responses by targeting Bcl-2. 11 Zhuang et al showed that miR-202 suppressed hepatocellular carcinoma progression via down-regulating Bcl-2 expression. 20 Here, we found that Bcl-2 over-expression reversed miR-21-induced apoptosis and inflammation, and showed synergic effects with miR-21 inhibitor in LPSinduced HPAEpiC.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-21 ameliorates LPS-induced acute lung injury through increasing B cell lymphoma-2 expression

Yao

Jia

et al. 2020

Innate Immun

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The aberrant expression of microRNAs (miRNAs) is associated with the pathogenesis of inflammation-related diseases. However, the biological functions of miR-21 in acute lung injury (ALI) remain largely unknown. In this study, the level of miR-21 was obviously increased, but B cell lymphoma-2 (Bcl-2) expression was markedly decreased in LPS-treated human pulmonary alveolar epithelial cells (HPAEpiC). Suppression of miR-21 attenuated LPS-induced apoptosis and inflammation in HPAEpiC and promoted the survival of mice with ALI by decreasing the inflammatory cell count, release of cytokines and permeability in lung tissues. Importantly, Bcl-2 was a direct target of miR-21, and its expression was significantly inhibited by miR-21 mimics at a post-transcriptional level. Besides, Bcl-2 over-expression reversed miR-21-induced apoptosis and inflammation status and showed synergic effects with miR-21 inhibitor in LPS-treated HPAEpiC. In conclusion, inhibition of miR-21 could ameliorate apoptosis and inflammation by restoring the expression of Bcl-2 in LPS-induced HPAEpiC and mice, which might provide therapeutic strategies for the treatment of ALI.

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MiR‐21‐5p regulates mycobacterial survival and inflammatory responses by targeting Bcl‐2 and TLR4 in Mycobacterium tuberculosis‐infected macrophages

Cited by 39 publications

References 21 publications

Unraveling the Role of MicroRNAs in Mycobacterium tuberculosis Infection and Disease: Advances and Pitfalls

Unraveling the Role of MicroRNAs in Mycobacterium tuberculosis Infection and Disease: Advances and Pitfalls

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

Inhibition of miR-21 ameliorates LPS-induced acute lung injury through increasing B cell lymphoma-2 expression

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