MAPK interacting serine/threonine kinase 1 ( MKNK1 ), one target gene of miR-223-3p, correlates with neutrophils in sepsis based on bioinformatic analysis

Abstract

Sepsis, resulting from a harmful or damaging response to infection, is a complex and severe disease that causes high mortality. Three independent expression profiles of miRNA -GSE94717, GSE149764, and GSE101639 -were collected and integrated to analyze miRNAs associated with sepsis. One miRNA, miR-223-3p, was detected significantly downregulated in patients with sepsis. The upregulated miR-223-3p target genes in patients with sepsis were enriched in central carbon metabolism associated with HIF-1 signaling and galactose metabolism. Specially, three HIF-1 signaling genes -hypoxia-inducible factor 1-alpha (HIF1A), hexokinase 2 (HK2), and MAP kinaseinteracting serine/threonine-protein kinase 1 (MKNK1) -were found significantly upregulated in patients with sepsis. Additionally, MKNK1 expression was downregulated in septic responders to early therapeutic treatments. Neutrophils were significantly accumulated in patients with sepsis and decreased in responders after therapy; MKNK1 was significantly positively correlated with neutrophils. Our findings indicate MKNK1, one targets of miR-223-3p, might be involved in sepsis via regulating the neutrophils abundance by mediating the expression inflammation factors.

The Regulatory Role of MicroRNAs on Phagocytes: A Potential Therapeutic Target for Chronic Diseases

“…Furthermore, neutrophils promote vascular inflammation and atherosclerosis by delivering miR-155-carrying microvesicles to disease-prone areas ( 139 ). Downregulation of miR-223-3p promotes the expression of mitogen-activated protein kinase (MAPK)-interacting serum/threonine kinase 1 (MKNK 1), which regulates the abundance of neutrophil-expressed inflammatory factors involved in sepsis ( 135 ).…”

“…However, it is not difficult to find from the foregoing that most of the current effects of miRNAs are concentrated in a certain part of a specific disease. For example, miR-223-3p is anti-inflammatory in the context of sepsis ( 135 ) while pro-inflammatory in the context of COPD ( 147 ). We can conclude from this that the effects of miRNAs are environment-specific, that is, the functions of miRNAs on neutrophils and macrophages are highly dependent on surrounding environmental factors, which makes miRNAs have inevitable side effects.…”

MicroRNA‐214‐3p facilitates M2 macrophage polarization by targeting GSK3B

“…MicroRNAs (miRNAs) are noncoding RNAs 22–24 nucleotides in length that exist widely in multicellular organisms 11 . MiRNAs modulate gene expression to affect the stability and translation of target mRNAs at the posttranscriptional level 12 . Accumulating studies have revealed the involvement of various miRNAs in AR development 13 .…”

“…11 MiRNAs modulate gene expression to affect the stability and translation of target mRNAs at the posttranscriptional level. 12 Accumulating studies have revealed the involvement of various miRNAs in AR development. 13 MiR-31 is downregulated in AR nasal mucosa, and miR-31 upregulation attenuates nasal rubbing, sneezing and IL-13-induced nasal epithelial inflammation during AR pathogenesis.…”