A comprehensive review on miR-146a molecular mechanisms in a wide spectrum of immune and non-immune inflammatory diseases

Mortazavi-Jahromi, Seyed Shahabeddin; Aslani, Mona; Mirshafiey, Abbas

doi:10.1016/j.imlet.2020.07.008

Cited by 35 publications

(30 citation statements)

References 257 publications

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“…According to bioinformatics analyses predicted by miRNASNP-v3 ( http://bioinfo.life.hust.edu.cn/miRNASNP/ ) and a previous study 27 , 38 , the 29940 G-to-C mutation in the 3′-UTR of NLRP3 might establish a new functional binding site for miR-146a-5p, which contributes to potential miR-146-5p recruitment and binding. Research so far has demonstrated an anti-inflammatory effect of miR-146a-5p on the regulation of multiple signaling pathways involved in the modulation of various inflammation-related cytokines 44 . Our results showed that miR-146a-5p expression was significantly downregulated under a sepsis or in vitro LPS stimulation, in accordance with the findings of our previous study 45 .…”

Section: Discussionmentioning

confidence: 99%

A gain-of-function NLRP3 3′-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression

Chen²,

Hong

et al. 2021

Sci Rep

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Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genotype/allelic frequencies of NLRP3 29940G>C between sepsis cases and controls. The G allele was significantly overrepresented in patients with septic shock than those in sepsis subgroup, and the GC/GG genetypes were related to the 28-day mortality of sepsis. Lipopolysaccharide challenge to peripheral blood mononuclear cells showed a significant suppression of NLRP3 mRNA expression and release of IL-1β and TNF-α in CC compared with the GC/GG genotype category. Functional experiments with luciferase reporter vectors containing the NLRP3 3′-UTR with the 29940 G-to-C variation in HUVECs and THP-1 cells showed a potential suppressive effect of miR-146a on NLRP3 transcription in the presence of the C allele. Taken together, these results demonstrated that the 29940 G-to-C mutation within the NLRP3 3′-UTR was a gain-of-function alteration that caused the suppression of NLRP3 expression and downstream inflammatory cytokine production via binding with miR-146a, which ultimately protected patients against susceptibility to sepsis progression and poor clinical outcome.

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Section: Discussionmentioning

confidence: 99%

A gain-of-function NLRP3 3′-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression

Chen²,

Hong

et al. 2021

Sci Rep

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“…These evolutionary conserved small RNAs, controlling the expression of 60% of human genes, participate in most of the biological processes including cellular proliferation, differentiation, maturation, activation, survival/apoptosis, and metabolism. miRNAs also have crucial roles in inflammatory/antiviral responses and the interaction between host and virus [6] , [15] , [16] , [17] , [20] , [97] , [98] , [99] , [100] . Over than 2000 miRNAs have been identified in the human, each of which has several target molecules.…”

Section: Mirnasmentioning

confidence: 99%

“…miRNAs exist in diverse forms including extracellular/circular (in the body fluids), intracellular ( i.e. cytoplasmic, nuclear, and organellic), and exosomal [17] , [97] . Their biogenesis is predominantly accomplished through the Canonical pathway, during which primary miRNAs (pri-miRNAs) and then precursor miRNAs (pre-miRNAs) are produced in the nucleus following the activity of RNA pol II/III and Drosha.…”

Section: Mirnasmentioning

confidence: 99%

“…In the next step, mature miRNAs are loaded on argonaute (AGO) resulting in the formation of the miRNA-induced silencing complex (miRISC). It is then directed toward the target mRNAs and modulates their expression [17] , [97] , [103] . In most cases, miRNAs interact with the 3'-UTR of different target mRNAs.…”

Section: Mirnasmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs performing as post-transcriptional regulators of genes expression [6] , [15] , [16] . These molecules bind to the 3'-untranslated region (3'-UTR) of their target messenger RNAs (mRNAs) and influence their expression [6] , [15] , [17] , [18] . Although it has been shown that some Homo sapiens (hsa)-miRNAs may be capable to target the SARS-CoV-2 genome, and some others can respectively regulate and augment inflammatory and type I IFNs (IFNs-I)-related pathways ( Fig.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cytokine storm in the pathophysiology of COVID-19: Possible functional disturbances of miRNAs

Aslani

Mortazavi-Jahromi

Mirshafiey

2021

International Immunopharmacology

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SARS-CoV-2, as the causative agent of COVID-19, is an enveloped positives-sense single-stranded RNA virus that belongs to the Beta-CoVs sub-family. A sophisticated hyper-inflammatory reaction named cytokine storm is occurred in patients with severe/critical COVID-19, following an imbalance in immune-inflammatory processes and inhibition of antiviral responses by SARS-CoV-2, which leads to pulmonary failure, ARDS, and death. The miRNAs are small non-coding RNAs with an average length of 22 nucleotides which play various roles as one of the main modulators of genes expression and maintenance of immune system homeostasis. Recent evidence has shown that Homo sapiens (hsa)-miRNAs have the potential to work in three pivotal areas including targeting the virus genome, regulating the inflammatory signaling pathways, and reinforcing the production/signaling of IFNs-I. However, it seems that several SARS-CoV-2-induced interfering agents such as viral (v)-miRNAs, cytokine content, competing endogenous RNAs (ceRNAs), etc. preclude efficient function of hsa-miRNAs in severe/critical COVID-19. This subsequently leads to increased virus replication, intense inflammatory processes, and secondary complications development. In this review article, we provide an overview of hsa-miRNAs roles in viral genome targeting, inflammatory pathways modulation, and IFNs responses amplification in severe/critical COVID-19 accompanied by probable interventional factors and their function. Identification and monitoring of these interventional elements can help us in designing the miRNAs-based therapy for the reduction of complications/mortality rate in patients with severe/critical forms of the disease.

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Indirect influence of microRNA‐146a on the association of IL‐6 and TNF‐α genetic polymorphisms with the increased risk of hip osteoarthritis

Tudor,

Baranasic,

Knezevic

et al. 2024

Journal Orthopaedic Research

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Primary osteoarthritis (POA) is a complex hereditary disease that involves the interplay between genetics and epigenetics. MicroRNA molecules play important roles in epigenetic mechanisms. MicroRNA‐146a (miR‐146a) is a negative regulator of the immune response in osteoarthritis (OA). So, variations in the miR‐146a gene could affect OA risk. The aim of this study was to investigate the relationships between single nucleotide polymorphisms (SNPs) in the miR‐146a, interleukin‐6 (IL‐6), Toll‐like receptor 10 (TLR10), and tumor necrosis factor‐alpha (TNFA) genes and the risk for development of advanced‐stage primary hip osteoarthritis (PHOA) and primary knee osteoarthritis (PKOA) in the Croatian population. A total of 609 POA patients and 656 healthy donors were genotyped for SNPs in the miR‐146a (rs2910164, G>C). Since we used same patients and controls as two studies before us, we already had information about IL‐6 (rs1800795, C>G), TLR10 (rs11096957, C>T), and TNFA (rs1800629, C>T) genotypes of our subjects. None of the differences were statistically significant comparing either allelic or genotypic frequencies of miR‐146a SNP rs2910164 (G>C) between the PHOA and PKOA patients and controls. However, we found a significant association with risk to PHOA for the combination of genotypes (stratified miR‐146a genotype with the IL‐6, and stratified miR‐146a genotype with the TNFA). In a multifactorial disease such as POA, we have shown the indirect relevance of a second modifying factor (miR‐146a), which apparently contributes to the overall risk of PHOA. There was no risk association with the PKOA, indicating that these two localities (hip and knee) might have different risk‐modifying factors.

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A comprehensive review on miR-146a molecular mechanisms in a wide spectrum of immune and non-immune inflammatory diseases

Cited by 35 publications

References 257 publications

A gain-of-function NLRP3 3′-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression

A gain-of-function NLRP3 3′-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression

Cytokine storm in the pathophysiology of COVID-19: Possible functional disturbances of miRNAs

Indirect influence of microRNA‐146a on the association of IL‐6 and TNF‐α genetic polymorphisms with the increased risk of hip osteoarthritis

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