The emerging role of miR-223 as novel potential diagnostic and therapeutic target for inflammatory disorders

Aziz, Faisal

doi:10.1016/j.cellimm.2016.04.003

Cited by 82 publications

(61 citation statements)

References 47 publications

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“…Three of these genes, neutrophil cytosolic factor 1, myeloperoxidase and IKKa, were predicted to have target sites to five of the DE miRNAs. One of the miRNAs (miR-223-5p) predicted to target IKKa has also been reported as targeting this gene in other vertebrates [43]. …”

Section: Resultsmentioning

confidence: 99%

“…One of the miRNAs (miR-223-5p) predicted to target IKKa has also been reported as targeting this gene in other vertebrates [43]. …”

Section: Resultsmentioning

confidence: 99%

“…These miRNAs showed target matches to nine and eight of the genes, respectively (Table 2). The miRNA showing largest number of target gene matches (miRNA-223) has been suggested as a diagnostic marker for inflammation in vertebrates [43]. Two of the mature miRNAs, ssa-miR-462a-3p and miR-731-5p, that originate from the same miRNA gene cluster [25], were both predicted to target the 3’UTR of the same gene (macrosialin, Table 2).…”

Section: Resultsmentioning

confidence: 99%

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Identification of differentially expressed Atlantic salmon miRNAs responding to salmonid alphavirus (SAV) infection

et al. 2017

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BackgroundMicroRNAs (miRNAs) control multiple biological processes including the innate immune responses by negative post-transcriptional regulation of gene expression. As there were no studies on the role(s) of miRNAs in viral diseases in Atlantic salmon, we aimed to identify miRNAs responding to salmonid alphavirus (SAV) infection. Their expression were studied at different time points post infection with SAV isolates associated with different mortalities. Furthermore, the genome sequences of the identified miRNAs were analysed to reveal putative cis-regulatory elements, and, finally, their putative target genes were predicted.ResultsTwenty differentially expressed miRNAs (DE miRNAs) were identified. The expression of the majority of these increased post infection with maximum levels reached after the viral load were stabilized or decreasing. On the other hand, some miRNAs (e.g. the miRNA-21 family) showed decreased expression at the early time points post infection. There were significant differences in the temporal expression of individual miRNA associated with different SAV isolates. Target gene prediction in SAV responsive immune network genes showed that seventeen of the DE miRNAs could target 24 genes (e.g. IRF3, IRF7). Applying the Atlantic salmon transcriptome as input 28 more immune network genes were revealed as putative targets (e.g. IRF5, IRF4). The majority of the predicted target genes promote inflammatory response. The upstream sequences of the miRNA genes revealed a high density of cis-regulatory sequences known as binding sites for immune network transcription factors (TFs). A high expression in the late phase could therefore be due to increased transcription promoted by immune response activated TFs. Based on the in silico target predictions, we discuss their putative roles as early promotors or late inhibitors of inflammation. We propose that the differences in expressions associated with different SAV isolates could contribute to their differences in mortality rates.ConclusionsThis study represents the first steps in exploring miRNAs important in viral-host interaction in Atlantic salmon. We identified several miRNAs responding to SAV infection. Some likely to prohibit harmful inflammation while other may promote an early immune response. Their predicted functions need to be validated and further studied in functional assays to fully understand their roles in immune homeostasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3741-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

“…One of the miRNAs (miR-223-5p) predicted to target IKKa has also been reported as targeting this gene in other vertebrates [43]. …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Identification of differentially expressed Atlantic salmon miRNAs responding to salmonid alphavirus (SAV) infection

et al. 2017

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“…The notable exception was high levels of miR-223, a hematopoietic-specific miRNA, which is abundantly expressed in PMNs (31). miR-223 is associated with down-regulation of acute inflammation (32) and tissue remodeling (33). This finding is consistent with high levels of PMNs present in SF from these patients.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA Expression Shows Inflammatory Dysregulation and Tumor‐Like Proliferative Responses in Joints of Patients With Postinfectious Lyme Arthritis

Lochhead

Strle

Kim

et al. 2017

Arthritis & Rheumatology

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Objective Lyme arthritis (LA) is caused by infection with Borrelia burgdorferi and usually resolves following spirochetal killing with antibiotics. However, in some patients, arthritis persists after antibiotic therapy. To provide insights into underlying pathogenic processes associated with post-infectious LA, we analyzed differences in microRNA expression between LA patients with active infection compared with those with post-infectious LA. Methods MicroRNA expression was assayed in synovial fluid (SF) from LA patients before and after oral and IV antibiotic therapy, and from synovial tissue from post-infectious LA patients obtained months after antibiotic therapy. SF and tissue from patients with other forms of arthritis such as rheumatoid arthritis and osteoarthritis were used for comparison groups. Results SF from LA patients during active infection had marked elevation in white blood cells, particularly polymorphonuclear leukocytes, accompanied by elevated miR-223 levels. In contrast, SF from post-antibiotic LA patients contained greater percentages of lymphocytes and mononuclear cells. Post-antibiotic LA SF also exhibited marked inflammatory (miR-146a, miR-155), wound repair (miR-142), and proliferative (miR-17~92) microRNA signatures, and higher levels of these microRNAs correlated with longer arthritis duration. miR-146a, miR-155, miR-142, miR-223, and miR-17~92 were also elevated in synovial tissue in late post-infectious LA, and let-7a was reduced, similar to RA. Conclusions During active infection, microRNA expression in SF reflected an immune response associated with bacterial killing, whereas in post-infectious LA, microRNA expression in SF and synovial tissue reflected chronic inflammation, synovial proliferation, and breakdown of wound repair processes, showing that the nature of the arthritis was altered after spirochetal killing.

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“…Of note, NLRP3 expression is negatively regulated on posttranscriptional level by the myeloid-specific micro-RNA (miR-)223 [58]. miR-223 has been attributed potent anti-inflammatory function in macrophages [59] as a consequence of inhibition of TF belonging to the NF-κB, C/EBP and STAT (signal transducer and activator of transcription) families [60]. …”

Section: Production Of Il-1β Requires Two Distinct Signalsmentioning

confidence: 99%

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Bent

Moll

Grabbe

et al. 2018

IJMS

319

221

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Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.

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The emerging role of miR-223 as novel potential diagnostic and therapeutic target for inflammatory disorders

Cited by 82 publications

References 47 publications

Identification of differentially expressed Atlantic salmon miRNAs responding to salmonid alphavirus (SAV) infection

Identification of differentially expressed Atlantic salmon miRNAs responding to salmonid alphavirus (SAV) infection

MicroRNA Expression Shows Inflammatory Dysregulation and Tumor‐Like Proliferative Responses in Joints of Patients With Postinfectious Lyme Arthritis

Interleukin-1 Beta—A Friend or Foe in Malignancies?

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