MicroRNAs as New Regulators of Neutrophil Extracellular Trap Formation

Abstract

Neutrophil extracellular traps (NETs) are formed after neutrophils expelled their chromatin content in order to primarily capture and eliminate pathogens. However, given their characteristics due in part to DNA and different granular proteins, NETs may induce a procoagulant response linking inflammation and thrombosis. Unraveling NET formation molecular mechanisms as well as the intracellular elements that regulate them is relevant not only for basic knowledge but also to design diagnostic and therapeutic tools that may prevent their deleterious effects observed in several inflammatory pathologies (e.g., cardiovascular and autoimmune diseases, cancer). Among the potential elements involved in NET formation, several studies have investigated the role of microRNAs (miRNAs) as important regulators of this process. miRNAs are small non-coding RNAs that have been involved in the control of almost all physiological processes in animals and plants and that are associated with the development of several pathologies. In this review, we give an overview of the actual knowledge on NETs and their implication in pathology with a special focus in cardiovascular diseases. We also give a brief overview on miRNA biology to later focus on the different miRNAs implicated in NET formation and the perspectives opened by the presented data.

The Significance of Neutrophil Extracellular Traps in Colorectal Cancer and Beyond: From Bench to Bedside

“…In addition to the abovementioned factors, microRNAs (miRNAs), a type of small non-coding RNAs that are involved in almost all physiological processes in the human body, modulate the process of NETosis ( 46 , 47 ). Arroyo et al.…”

Dysregulated miRNAs network in the critical COVID-19: An important clue for uncontrolled immunothrombosis/thromboinflammation

“…The CC genotype of miR-SNP rs2910164 (located in the stem region opposite to mature miR-146a sequence) and the A/G genotype of miR-SNP rs57095329 (located in the promoter region of the miR-146a gene) are the two other SNPs in the miR-146a gene that can decrease its expression. The existence of the A/T allele of miR-SNP rs767649 (located in the regulation region of the miR-155 gene) can underlie the elevated transcriptional activity of this gene [183] , [242] , [243] , [244] , [245] , [246] , [247] ( Table 1 ). Moreover, the reduced expressions of miR-143 and miR-145 have respectively been reported in the carriers of CT/TT variant of miR-SNP rs353292 (located 673 bp upstream from the start site) and C/T variant of miR-SNP rs74693964 (located 65 bp downstream of the miR-145 genomic region) [248] , [249] ( Table 1 ).…”

Current Understanding of the Neutrophil Transcriptome in Health and Disease

“…NETosis, the process of NET formation, is also transcriptionally dependent, as demonstrated by the ability of the global transcription inhibitor actinomycin D to almost completely suppress NETosis [54]. Key to regulating the formation of NETs from this transcriptional activity are the miRNAs miR-155, miR-146a, miR-505 and miR-378a-3p [87]. These can be from endogenous miRNAs or exogenous miRNAs from exosomes of macrophage and tissue cells, or activated platelets [87].…”

“…Key to regulating the formation of NETs from this transcriptional activity are the miRNAs miR-155, miR-146a, miR-505 and miR-378a-3p [87]. These can be from endogenous miRNAs or exogenous miRNAs from exosomes of macrophage and tissue cells, or activated platelets [87].…”