miR-20a Inhibits TCR-Mediated Signaling and Cytokine Production in Human Naïve CD4+ T Cells

Reddycherla, Amarendra V.; Meinert, Ines; Reinhold, Annegret; Reinhold, Dirk; Schraven, Burkhart; Simeoni, Luca

doi:10.1371/journal.pone.0125311

Cited by 29 publications

(18 citation statements)

References 57 publications

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“…Asterisks indicate whether there were significant differences among the groups. *P < 0.05; **P < 0.01. www.nature.com/scientificreports www.nature.com/scientificreports/ was detected; (iii) and previously published data regarding the miRNAs profile in decompensated cirrhosis 17,18 , inflammation 19,20 , and sepsis [21][22][23] .…”

Section: Discussionmentioning

confidence: 77%

“…Based on the magnitude of expression difference between patients with and without ACLF in the microarray analysis and in literature reports [17][18][19][20][21][22][23] miRNAs miR-106b-5p, miR-126-3p, miR-20a-5p, miR-223-3p, and miR-25-3p were selected to be further validated by RT-qPCR. Some miRNAs that had high FC values such as let-7a-5p and let-7g-5p were not detected in most microarray samples and were therefore not included in the validation step.…”

Section: Resultsmentioning

confidence: 99%

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MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction

Cisilotto

Amaral

Rosolen

et al. 2020

Sci Rep

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Acute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of cirrhosis, associated with organ failure(s), and high short-term mortality. The microRNAs or miRNAs are small non-coding RNA molecules, stable in circulating samples such as biological fluids, and the difference in expression levels may indicate the presence, absence and/or stage of the disease. We analyzed here the miRNA profiling to identify potential diagnostic or prognostic biomarkers for ACLF. The major miRNAs discovered were validated in a cohort of patients with acute decompensation of cirrhosis grouped in no ACLF or ACLF according to EASL-CLIF definition. Relationship between serum miRNAs and variables associated with liver-damage and survival outcomes were verified to identify possible prognostic markers. Our results showed twenty altered miRNAs between no ACLF and ACLF patients, and twentyseven in patients who died in 30 days compared with who survived. In validation phase, miR-223-3p and miR-25-3p were significantly altered in ACLF patients and in those who died in 30 days. miR-223-3p and miR-25-3p expression were associated with the lowest survival in 30 days. The decrease in miR-223-3p and miR-25-3p expression was associated with the presence of ACLF and poor prognosis. Of these, miR-25-3p was independently related to ACLF and 30-day mortality. The natural history of cirrhosis is usually characterized by a long-standing compensated phase followed by a transition to the decompensated disease, identified by the occurrence of specific complications of cirrhosis, such as ascites, variceal bleeding, and hepatic encephalopathy 1. Patients with both compensated or decompensated cirrhosis are at risk of progression to acute-on-chronic liver failure (ACLF), a condition characterized by an acute deterioration of the liver function and characterized by progression to extrahepatic organ failure and high short-term mortality 2,3. Although a precise definition is still lacking, the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium definition is one of the most validated criteria for ACLF in patients with cirrhosis and it is based on a modified version of SOFA score called CLIF-SOFA 2,4. According to a recently published study 5 , mortality rates in ACLF patients are 25.5% and 40% in 28 and 90 days of admission, respectively. Therefore, searching for new biomarkers associated with the presence of ACLF and prognosis of patients with acute decompensation of cirrhosis may improve clinical decision and help to implement risk-adapted treatment strategies. In recent years, miRNAs have been studied as promising biomarkers for the diagnosis and prognostic in many clinical scenarios 6-8 , including liver diseases 9. The miRNAs are a group of small non-coding RNAs, with approximately 22 nucleotides, which post-transcriptionally regulate gene expression

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Section: Discussionmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 99%

MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction

Cisilotto

Amaral

Rosolen

et al. 2020

Sci Rep

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“…Moreover, miR-20a is a member of the miR-17-92 cluster which has been demonstrated to play important roles in various biological processes including oncogenicity (Wang Z. et al, 2015 ), immune regulation (Cox et al, 2010 ), and disease progression (Sasaki et al, 2010 ). It is reported that miR-20a inhibits TCR-mediated signaling and cytokine production in human naïve CD4 + T cells (Reddycherla et al, 2015 ). Zhu et al have demonstrated that a panel of miRNAs including miR-20a, miR-17, and miR-106a can regulate macrophage inflammatory responses by targeting signal-regulatory protein α (Zhu et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

microRNA-20a Inhibits Autophagic Process by Targeting ATG7 and ATG16L1 and Favors Mycobacterial Survival in Macrophage Cells

Guo

Zhao

et al. 2016

Front. Cell. Infect. Microbiol.

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Autophagy plays important roles in the host immune response against mycobacterial infection. Mycobacterium tuberculosis (M. tuberculosis) can live in macrophages owing to its ability to evade attacks by regulating autophagic response. MicroRNAs (miRNAs) are small noncoding, endogenously encoded RNA which plays critical roles in precise regulation of macrophage functions. Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that BCG infection of macrophages resulted in enhanced expression of miRNA-20a, which inhibits autophagic process by targeting ATG7 and ATG16L1 and promotes BCG survival in macrophages. Forced overexpression of miR-20a decreased the expression levels of LC3-II and the number of LC3 puncta in macrophages, and promoted BCG survival in macrophages, while transfection with miR-20a inhibitor had the opposite effect. Moreover, the inhibitory effect of miR-20a on autophagy was further confirmed by transmission electron microscopy (TEM) analysis. Quantification of autophagosomes per cellular cross-section revealed a significant reduction upon transfection with miR-20a mimic, but transfection with miR-20a inhibitor increased the number of autophagosomes per cellular cross-section. Moreover, silencing of ATG7 significantly inhibited autophagic response, and transfection with ATG7 siRNA plus miR-20a mimic could further decrease autophagic response. Collectively, our data reveal that miR-20a inhibits autophagic response and promotes BCG survival in macrophages by targeting ATG7 and ATG16L1, which may have implications for a better understanding of pathogenesis of M. tuberculosis infection.

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“…Finally, the upregulation of miR-21 could be sustained by the contextual downregulation of miR-20a that could contribute to the lack of an anti-inflammatory property [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miRNA17–92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis

et al. 2018

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BackgroundWe aimed to evaluate the phenotype, function, and microRNA (miRNA)17–92 cluster expression in Vγ9Vδ2 T-cell subsets and the correlation with immune response in rheumatoid arthritis (RA) patients.MethodsPeripheral blood from 10 early RA untreated patients and 10 healthy donors (HD) was obtained. Polyclonal Vγ9Vδ2 T-cell lines were generated and analysed by flow cytometry. Analysis of miRNA17–92 cluster expression was performed by real-time polymerase chain reaction (RT-PCR), and expression of mRNA target genes was also studied.ResultsA remarkable change in the distribution of Vγ9Vδ2 T-cell functional subsets was observed in the peripheral blood of RA patients compared with HD, with an expansion of effector subsets and reduction of naive cells which was accompanied by modifications in proinflammatory cytokine expression. Vγ9Vδ2 T cells with a TEM (effector memory) phenotype and producing proinflammatory cytokines were correlated with disease activity score (DAS28). The comparison of miRNA expression among Vγ9Vδ2 T-cell subsets from RA patients and HD showed a lower level of miR-106a-5p and miR-20a-5p, and a higher level of miR-21a-5p, among Vγ9Vδ2 TEM cells, and a lower level of miR-19b-3p among Vγ9Vδ2 TCM (central memory) cells was also found. These differentially expressed miRNAs correlated with higher levels of expression of interleukin (IL)-8, IL-6, and PDCD4 genes.ConclusionsOur results provide evidence for a role of miR-106a, miR-19-3p, miR-20a, and miR-21a in the regulation of Vγ9Vδ2 T-cell function in RA patients and suggest the possibility that the miRNA17–92 family and Vγ9Vδ2 T cells contribute to the pathogenesis of RA.

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miR-20a Inhibits TCR-Mediated Signaling and Cytokine Production in Human Naïve CD4+ T Cells

Cited by 29 publications

References 57 publications

MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction

MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction

microRNA-20a Inhibits Autophagic Process by Targeting ATG7 and ATG16L1 and Favors Mycobacterial Survival in Macrophage Cells

Downregulation of miRNA17–92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis

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