MiRNA-133a aggravates inflammatory responses in sepsis by targeting SIRT1

Chen, Lei; Xie, Wenli; Wang, Lichun; Zhang, Xiaofei; Liu, Enhe; Kou, Qiuye

doi:10.1016/j.intimp.2020.106848

Cited by 32 publications

(28 citation statements)

References 30 publications

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“… 32 Reducing the SITR1 inhibitive effect of miR-133a on LPS-induced sepsis was reversed. 33 Shikonin, a traditional Chinese medicine extract, improved LPS-induced sepsis cardiac dysfunction by SIRT1. 34 We predicted that SIRT1 was the target gene of miR-486-5p through the online biological software miRDB, and miR-486-5p targeting SIRT1 has been demonstrated in non-small cell lung cancer 35 and myocardial ischemia-reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

Sun

Guo

2021

JIR

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Background As a molecular detection method, miRNA can quickly diagnose and prevent diseases, intervene in disease as early as possible, and reduce mortality. This study was to investigate the potential clinical diagnostic and predictive significance of miR-486-5p in sepsis and its correlation with inflammation and disease severity. Methods The serum miR-486-5p in 108 sepsis, 60 pneumonia-infected, and 101 healthy controls were detected by RT-qPCR. Spearman coefficient detects the correlation between serum miRNA and disease severity indicators (APACHE II, SOFA scores), and inflammation indicators (CRP, PCT), respectively. The diagnostic significance of miR-486-5p in sepsis was analyzed by the ROC curve. Kaplan–Meier estimator and Cox regression hazards analysis of the predictive significance of serum miR-486-5p in 28-day survival from sepsis. Results Serum miR-486-5p was increased in sepsis patients compared with healthy control and pneumonia-infected patients ( P < 0.001). And increased serum miR-486-5p was positively associated with disease severity (SOFA score and APACHE II score) and inflammation (CRP and PCT). Serum miR-486-5p can not only identify sepsis patients from healthy controls (AUC = 0.914) but also significantly distinguish sepsis patients from pneumonia-infected patients (AUC = 0.814), showing good potential as a diagnostic biomarker for sepsis. In addition, serum miR-486-5p was an independent predictor of 28-day survival (log-rank P = 0.012), and patients with high levels of miR-486-5p had a poorer overall 28-day survival (HR = 3.057, 95% CI = 1.385–17.817, P = 0.014). Conclusion miR-486-5p is a potential diagnostic biomarker for sepsis, and its high level is significantly correlated with the disease severity and inflammation. In addition, miR-486-5p were predictive risk factors for 28-day survival in sepsis patients.

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Section: Discussionmentioning

confidence: 99%

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

Sun

Guo

2021

JIR

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“…A large number of studies have shown that miRNAs participate in the regulation of host cytokine storm after virus invasion. For example, after influenza virus invasion, miR-302a can induce cytokine storm, and miR-133a also has the same effect 31,32 . Interestingly, we found that miR-126-5p significantly inhibits the expression of inflammatory cytokines related genes after NDV virus infection.…”

Section: Discussionmentioning

confidence: 99%

Chicken miR-126-5p Negatively Regulates Antiviral Innate Immunity By Targeting TRAF3

Wang

Cheng

Wang

et al. 2021

Preprint

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Background Innate immunity plays an essential role in preventing the invasion of pathogenic microorganisms. However, innate immunity is a double-edged sword, whose excessively activated is detrimental to immune homeostasis and even leads to "cytokine storm" of the infected host. A series of negative regulatory mechanisms are developed by the host to balance the immune response. Here, we report a negative regulatory mechanism of chicken innate immunity mediated by miRNA. Results In this study we found that the miR-126-5p is markedly up-regulated in RNA virus infected chickens in GEO database. Then, the upregulation of the miR-126-5p by RNA virus was further verified via both cell model and in vivo test. Overexpression of miR-126-5p significantly inhibits the expression of interferon related genes and inflammatory cytokines evoked by RNA virus. The opposite result was achieved after knocking down miR-126-5p expression. Bioinformatics analysis indicated TRAF3 as the candidate target gene of miR-126-5p, and experimental evidence, such as the effects of miR-126-5p on the endogenous expression of TRAF3, and the effect of miR-126-5p on TRAF3 3'UTR drove luciferase reporter assay, were provided to further verify that miR-126-5p targets TRAF3. Furthermore, we demonstrated that miR-126-5p negatively regulates innate immunity by blocking the MAVS-TRAF3-TBK1 axis, with co-expression assay. Conclusion Our results suggest that miR-126-5p is involved in the negative regulation of the chicken innate immunity, which might contribute to maintaining immune balance.

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“…* p < .05 4 | DISCUSSION miRNAs are implicated in the pathogenesis of sepsis-related cardiac, lung, liver and kidney disorders. 21,22,[31][32][33] This study aimed to ascertain a novel target for the treatment of sepsisinduced ALI. This study revealed that miR-942-5p limited TRIM37 expression and ameliorated LPS-induced ALI in vitro and inflammatory response in A549 cells.…”

Section: Trim37 Overexpression Attenuates the Protective Role Of 942-5p In Lps-treated A549 Cellsmentioning

confidence: 99%

“…9 miRNAs play regulatory roles in diverse physiological and pathological processes, such as cell proliferation and apoptosis, [10][11][12][13][14][15] tissue differentiation, 16 inflammation 17,18 and tumour formation. [10][11][12][13]19 In recent years, several lines of evidence suggest the pivotal roles of miRNA in sepsis, such as miR-223, 20 miR-133a 21,22 and miR-186. 23,24 miRNA-942-5p is shown to be involved in many cellular processes, such as tumour cell phenotypes, 6,12,23,24 osteogenic differentiation, 25,26 cardiomyocyte apoptosis, 27 and the oxidative stress and inflammatory response of vascular endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

miR‐942‐5p prevents sepsis‐induced acute lung injury via targeting TRIM37

Lü

Zhang

Liu

et al. 2021

Int J Experimental Path

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MicroRNAs (miRNAs) have been demonstrated to play pivotal roles in the pathogenesis of sepsis‐induced acute lung injury (ALI). In this work, we aimed to clarify the potential role and the underlying mechanism of miR‐942‐5p in a lipopolysaccharide (LPS)‐induced A549 cell injury model. The cell injury was evaluated by CCK‐8 assay, flow cytometry and enzyme‐linked immunosorbent assay (ELISA). The expression levels of miR‐942‐5p and tripartite motif‐containing protein 37 (TRIM37) were measured by real‐time PCR and Western blot, and their association was then validated by bioinformatics, luciferase reporter assay and RNA pull‐down assay. We found that the expression of miR‐942‐5p was decreased in LPS‐treated A549 cells. Furthermore, LPS treatment suppressed A549 cell viability, promoted apoptosis and increased the levels of inflammatory cytokines. Conversely, overexpression of miR‐942‐5p increased cell viability, reduced apoptosis and alleviated inflammatory cytokine secretion in the presence of LPS. Moreover, miR‐942‐5p directly targeted TRIM37 by binding to the 3′‐UTR of TRIM37 mRNA. Upregulation of TRIM37 effectively reversed the anti‐apoptotic and anti‐inflammatory effects of miR‐942‐5p in LPS‐induced A549 cells. Our findings suggested that miR‐942‐5p protected against LPS‐induced cell injury through inhibiting apoptosis and inflammation in A549 cells by negatively regulating TRIM37.

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MiRNA-133a aggravates inflammatory responses in sepsis by targeting SIRT1

Cited by 32 publications

References 30 publications

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

Chicken miR-126-5p Negatively Regulates Antiviral Innate Immunity By Targeting TRAF3

miR‐942‐5p prevents sepsis‐induced acute lung injury via targeting TRIM37

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