Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma

Owen, Helen; Torrance, Hew D.T.; Jones, Timothy F.; Pearse, Rupert M; Hinds, C. J.; Brohi, Karim; O’Dwyer, Michael J.

doi:10.1097/ta.0000000000000850

Cited by 14 publications

(13 citation statements)

References 21 publications

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“…Non-coding RNAs are abundant RNA molecules with limited ability to translate into proteins, and the imbalances of non-coding RNAs in human body have been implicated in pathology of a variety of human diseases. 19 As a type of functionally important non-coding RNA, long non-coding RNAs (lncRNAs) are defined as non-protein-coding transcripts with length longer than 200 nucleotides, which are recognized as key players in various biological processes including inflammation, angiogenesis, and oncogenesis. 6,7 The best well-known mechanism of lncRNAs is their ability to sequester endogenous RNAs such as microRNAs (miRNAs), which are a small non-coding RNA molecules around 22 nucleotides long, and regulate the downstream signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

LncRNA ANRIL/miR‐125a axis exhibits potential as a biomarker for disease exacerbation, severity, and inflammation in bronchial asthma

Zhu

Feng

2019

Clinical Laboratory Analysis

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Background This study aimed to explore the correlation of lncRNA ANRIL/miR‐125a axis with disease risk, severity, and inflammatory cytokines of bronchial asthma. Methods Plasma samples from 90 patients with bronchial asthma at exacerbation (BA‐E), 90 with bronchial asthma at remission (BA‐R), and 90 controls (healthy subjects) were collected. The qPCR was used for lncRNA ANRIL and miR‐125a detection, and ELISA was adopted for pro‐inflammatory cytokines detection. Participants’ characteristics, laboratory tests, and the pulmonary ventilation function examinations were recorded. Results LncRNA ANRIL was negatively correlated with miR‐125a in BA‐E patients, BA‐R patients, and controls. LncRNA ANRIL/miR‐125a axis was upregulated in BA‐E patients compared with BA‐R patients and controls. ROC curve analyses illuminated that lncRNA ANRIL/miR‐125a axis was of good value in distinguishing BA‐E patients from BA‐R patients and controls. As to pulmonary ventilation functions, lncRNA ANRIL/miR‐125a axis was negatively associated with FEV1/FVC and FEV1%predicted in bronchial asthma patients, especially in BA‐E patients. Regarding inflammation, lncRNA ANRIL/miR‐125a axis was positively correlated with pro‐inflammatory cytokines in bronchial asthma patients, especially in BA‐E patients. In addition, lncRNA ANRIL/miR‐125a axis was positively correlated with exacerbation severity in BA‐E patients. Conclusion LncRNA ANRIL/miR‐125a is potentially indicative of disease exacerbation, exacerbation severity, and inflammation for bronchial asthma, while these findings are preliminary and need further confirmation.

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Section: Discussionmentioning

confidence: 99%

LncRNA ANRIL/miR‐125a axis exhibits potential as a biomarker for disease exacerbation, severity, and inflammation in bronchial asthma

Zhu

Feng

2019

Clinical Laboratory Analysis

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“…MicroRNAs (miRNAs) are a highly conserved class of short single-stranded non-coding RNA molecules, which via translational repression or degradation of messenger RNA play an important role in regulating gene expression [ 34 ]. In rodents [ 35 – 37 ] and humans [ 38 , 39 ], traumatic injury leads to significant alterations in the circulating levels of miRNAs. For instance, when compared to healthy controls, the levels of circulating miRNAs predicted to regulate the expression of pro- and anti-inflammatory cytokine genes (e.g., miR-125a, miR-181, miR-202, miR-374b and miR454) as well as genes involved in neuronal survival and central nervous system signalling have been shown to be increased or decreased in samples obtained post-polytrauma or TBI [ 36 , 38 ].…”

Section: Reviewmentioning

confidence: 99%

The diagnostic and prognostic value of systems biology research in major traumatic and thermal injury: a review

2016

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As secondary complications remain a significant cause of morbidity and mortality amongst hospitalised trauma patients, the need to develop novel approaches by which to identify patients at risk of adverse outcome is becoming increasingly important. Centred on the idea that patients who experience “poor” outcome post trauma elicit a response to injury that is distinct from those who experience “good” outcome, tailored therapeutics is an emerging concept aimed at improving current treatment regimens by promoting patient-specific therapies. Making use of recent advancements in the fields of genomics, proteomics and metabolomics, numerous groups have undertaken a systems-based approach to analysing the acute immune and inflammatory response to major traumatic and thermal injury in an attempt to uncover a single or combination of biomarkers that can identify patients at risk of adverse outcome. Early results are encouraging, with all three approaches capable of discriminating patients with “good” outcome from those who develop nosocomial infections, sepsis and multiple organ failure, with differences apparent in blood samples acquired as early as 2 h post injury. In particular, genomic data is proving to be highly informative, identifying patients at risk of “poor” outcome with a higher degree of sensitivity and specificity than statistical models built upon data obtained from existing anatomical and physiological scoring systems. Here, focussing predominantly upon human-based research, we provide an overview of the findings of studies that have investigated the immune and inflammatory response to major traumatic and thermal injury at the genomic, protein and metabolite level, and consider both the diagnostic and prognostic potential of these approaches.

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“…Other studies indicate a physiological association between increases in follicular miRNA levels and hormone secretion levels in mammals, which involved signaling pathways involved in follicular cell proliferation, steroidogenesis, prevention of premature luteinization, and oocyte maturation (Sontakke et al, 2014;Donadeu et al, 2016;Xie et al, 2016). miR-202 inhibits tumor progression and (Farhana et al, 2015;Lin et al, 2016;Meng et al, 2016) affects the immune system (Fornari et al, 2015;Owen et al, 2015). miRNAs regulate levels of expression of target genes by controlling the signal pathways (Š ahmatova et al, 2016;Wang et al, 2016).…”

Section: Discussionmentioning

confidence: 94%

Differential Expression of miR-202 and Validation of Predicted Target Genes in the Skin Tissue of C57BL/6 Black Mice and BALB/c White Mice

Liu

Zhao

et al. 2017

DNA and Cell Biology

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In recent years, with the need of the fur industry to obtain greater quantities of high-quality fur and the research of hair follicle development attracting greater attention, the role of miRNAs in hair follicle development has become a field of intense interest. miRNAs are short length RNAs that affect gene regulation by binding to the 3'-untranslated region (3'UTR) of the mRNAs of certain target genes. This study predicted and validated the target genes of miR-202 in the skin tissue of C57BL/6 black mice and BALB/c white mice. The expression of miR-202 target genes (wnt5a, kit, and tcf7) was examined by real-time quantitative polymerase chain reaction and western blot in the mouse skin tissue and human embryonic kidney 293T cells (HEK293T cells) which overexpress miR-202. The luciferase reporter gene system was used to verify the correlation between the expression of miR-202 and its putative target genes. We show that the expression of miR-202 was higher in the skin tissue of C57BL/6 black mice than in the skin tissue of BALB/c white mice (p < 0.05). Furthermore, the expression of wnt5a, kit, and tcf7 was observed to be negatively correlated with the expression of miR-202 and to be downregulated by miR-202 in vitro and in vivo. The luciferase reporter gene system indicated that the target sequences of miR-202 are present in 3'UTR of wnt5a, kit, and tcf7 mRNAs. Altogether, this study has shown that the expression of miR-202 was different in the skin tissue of C57BL/6 black mice and BALB/c white mice and that wnt5a, kit, and tcf7 are negatively regulated by miR-202.

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Epigenetic regulatory pathways involving microRNAs may modulate the host immune response following major trauma

Abstract: Background: Post traumatic nosocomial pneumonia is a common complication resulting in

Cited by 14 publications

References 21 publications

LncRNA ANRIL/miR‐125a axis exhibits potential as a biomarker for disease exacerbation, severity, and inflammation in bronchial asthma

LncRNA ANRIL/miR‐125a axis exhibits potential as a biomarker for disease exacerbation, severity, and inflammation in bronchial asthma

The diagnostic and prognostic value of systems biology research in major traumatic and thermal injury: a review

Differential Expression of miR-202 and Validation of Predicted Target Genes in the Skin Tissue of C57BL/6 Black Mice and BALB/c White Mice

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