A comprehensive bioinformatics analysis Young-Aged Coronary Heart Disease

Abstract Background Coronary heart disease (CHD) is a leading cause of morbidity and mortality worldwide[1]. Although effective primary and secondary prevention successfully reduced the mortality of CHD, morbidity and mortality of young aged coronary heart disease (YA-CHD) didn’t decrease. However, little is known about the prevalence and mechanism of YA-CHD.Methods Dataset GSE 12288 from Gene Expression Omnibus was imported and performed comprehensive bioinformatics analysis, including gene ontology analysis (GO analysis), pathway analysis, protein-protein interaction network (PPI) analysis and core network analysis.Results RAP1A, which regulates platelet integrin activation and has a critical role in platelet production, was significantly up regulated, while TNKS2, which keeps the integrity of the leukocyte telomere structure and shows a significant association with longevity, was significantly downregulated. Biological process analysis showed “phagosome” pathway was mostly significant related to YA-CHD. Innate immune response module and type I interferon signaling module, interacts with IRF1, may major in the regulation of YA-CHD progression and maybe the potential therapeutic target of YA-CHD.Conclusions RAP1A and TNKS2 in peripheral leukocytes may serve as novel biomarkers in predicting the onset of YA-CHD. Further studies about weather IRF1 influence YA-CHD through regulating innate immune type I interferon signaling pathway was needed.

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Vitamin D Potentiates the Inhibitory Effect of MicroRNA-130a in Hepatitis C Virus Replication Independent of Type I Interferon Signaling Pathway

Mediators of Inflammation ◽

10.1155/2015/508989 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Xiaoqiong Duan ◽

Yujuan Guan ◽

Yujia Li ◽

Shan Chen ◽

Shilin Li ◽

...

Keyword(s):

Vitamin D ◽

Type I Interferon ◽

Inhibitory Effect ◽

Therapeutic Strategies ◽

Innate Immune ◽

Type I ◽

Interferon Signaling ◽

Host Innate Immune Response ◽

Antiviral Mechanism

Calcitriol, the bioactive metabolite of vitamin D, was reported to inhibit HCV production in a synergistic fashion with interferon, a treatmentin vitro. Our previous study established that miR-130a inhibits HCV replication by restoring the host innate immune response. We aimed to determine whether there is additive inhibitory effect of calcitriol and miR-130a on HCV replication. Here we showed that calcitriol potentiates the anti-HCV effect of miR-130a in both Con1b replicon and J6/JFH1 culture systems. Intriguingly, this potentiating effect of calcitriol on miR-130a was not through upregulating the expression of cellular miR-130a or through increasing the miR-130a-mediated IFNα/βproduction. All these findings may contribute to the development of novel anti-HCV therapeutic strategies although the antiviral mechanism needs to be further investigated.

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Activation of RIG-I-mediated antiviral signaling triggers autophagy through the MAVS-TRAF6-Beclin-1 signaling axis

10.1101/340323 ◽

2018 ◽

Cited By ~ 1

Author(s):

Na-Rae Lee ◽

Junsu Ban ◽

Noh-Jin Lee ◽

Chae-Min Yi ◽

Jiyoon Choi ◽

...

Keyword(s):

Type I Interferon ◽

Sendai Virus ◽

Feedback Mechanism ◽

Innate Immune ◽

Beclin 1 ◽

Interferon Response ◽

Type I ◽

Interferon Signaling ◽

Negative Feedback Mechanism ◽

Signaling Axis

AbstractAutophagy has been implicated in innate immune responses against various intracellular pathogens. Recent studies have reported that autophagy can be triggered by pathogen recognizing sensors, including Toll-like receptors and cyclic guanosine monophosphate-adenosine monophosphate synthase, to participate in innate immunity. In the present study, we examined whether the RIG-I signaling pathway, which detects viral infections by recognizing viral RNA, triggers the autophagic process. The introduction of polyI:C into the cytoplasm, or Sendai virus infection, significantly induced autophagy in normal cells but not in RIG-I-deficient cells. PolyI:C transfection or Sendai virus infection induced autophagy in the cells lacking type-I interferon signaling. This demonstrated that the effect was not due to interferon signaling. RIG-I-mediated autophagy diminished by the deficiency of mitochondrial antiviral signaling protein (MAVS) or tumor necrosis factor receptor-associated factor (TRAF)6, showing that the RIG-I-MAVS-TRAF6 signaling axis was critical for RIG-I-mediated autophagy. We also found that Beclin-1 was translocated to the mitochondria, and it interacted with TRAF6 upon RIG-I activation. Furthermore, Beclin-1 underwent K63-polyubiquitination upon RIG-I activation, and the ubiquitination decreased in TRAF6-deficient cells. This suggests that the RIG-I-MAVS-TRAF6 axis induced K63-linked polyubiquitination of Beclin-1, which has been implicated in triggering autophagy. Collectively, the results of this study show that the recognition of viral infection by RIG-I is capable of inducing autophagy to control viral replication. As deficient autophagy increases the type-I interferon response, the induction of autophagy by the RIG-I pathway might also contribute to preventing an excessive interferon response as a negative-feedback mechanism.ImportanceMammalian cells utilize various innate immune sensors to detect pathogens. Among those sensors, RIG-I recognizes viral RNA to detect intracellular viral replication. Although cells experience diverse physiological changes upon viral infection, studies to understand the role of RIG-I signaling have focused on the induction of type-I interferon. Autophagy is a process that sequesters cytosolic regions and degrades the contents to maintain cellular homeostasis. Autophagy participates in the immune system, and has been known to be triggered by some innate immune sensors, such as TLR4 and cGAS. We demonstrated that autophagy can be triggered by the activation of RIG-I. In addition, we also proved that MAVS-TRAF6 downstream signaling is crucial for the process. Beclin-1, a key molecule in autophagy, is translocated to mitochondria, where it undergoes K63-ubiquitination in a TRAF6-dependent manner upon RIG-I activation. As autophagy negatively regulates RIG-I-mediated signaling, the RIG-I-mediated activation of autophagy may function as a negative-feedback mechanism.

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Critical role for constitutive type I interferon signaling in the prevention of cellular transformation

Cancer Science ◽

10.1111/j.1349-7006.2008.01051.x ◽

2009 ◽

Vol 100 (3) ◽

pp. 449-456 ◽

Cited By ~ 37

Author(s):

Hui-min Chen ◽

Nobuyuki Tanaka ◽

Yukiko Mitani ◽

Eri Oda ◽

Hiroaki Nozawa ◽

...

Keyword(s):

Type I Interferon ◽

Critical Role ◽

Cellular Transformation ◽

Type I ◽

Interferon Signaling

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TRIM65-catalized ubiquitination is essential for MDA5-mediated antiviral innate immunity

Journal of Experimental Medicine ◽

10.1084/jem.20160592 ◽

2016 ◽

Vol 214 (2) ◽

pp. 459-473 ◽

Cited By ~ 56

Author(s):

Xueting Lang ◽

Tiantian Tang ◽

Tengchuan Jin ◽

Chen Ding ◽

Rongbin Zhou ◽

...

Keyword(s):

Innate Immunity ◽

Signaling Pathways ◽

Type I Interferon ◽

Critical Role ◽

Encephalomyocarditis Virus ◽

Type I ◽

Interferon Signaling ◽

Antiviral Innate Immunity ◽

Irf3 Activation

MDA5 plays a critical role in antiviral innate immunity by functioning as a cytoplasmic double-stranded RNA sensor that can activate type I interferon signaling pathways, but the mechanism for the activation of MDA5 is poorly understood. Here, we show that TRIM65 specifically interacts with MDA5 and promotes K63-linked ubiquitination of MDA5 at lysine 743, which is critical for MDA5 oligomerization and activation. Trim65 deficiency abolishes MDA5 agonist or encephalomyocarditis virus (EMCV)–induced interferon regulatory factor 3 (IRF3) activation and type I interferon production but has no effect on retinoic acid–inducible I (RIG-I), Toll-like receptor 3 (TLR3), or cyclic GMP-AMP synthase signaling pathways. Importantly, Trim65−/− mice are more susceptible to EMCV infection than controls and cannot produce type I interferon in vivo. Collectively, our results identify TRIM65 as an essential component for the MDA5 signaling pathway and provide physiological evidence showing that ubiquitination is important for MDA5 oligomerization and activation.

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Faculty Opinions recommendation of Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1165559.628567 ◽

2009 ◽

Author(s):

E Charles Snow

Keyword(s):

Dendritic Cells ◽

Lymph Node ◽

Type I Interferon ◽

Type I ◽

Interferon Signaling ◽

T Follicular Helper Cells ◽

Helper Cells ◽

Follicular Helper

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Faculty Opinions recommendation of Blockade of chronic type I interferon signaling to control persistent LCMV infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717999659.793474946 ◽

2013 ◽

Author(s):

Giorgio Trinchieri

Keyword(s):

Type I Interferon ◽

Type I ◽

Interferon Signaling ◽

Chronic Type ◽

Lcmv Infection

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Faculty Opinions recommendation of Persistent LCMV infection is controlled by blockade of type I interferon signaling.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717999658.793476087 ◽

2013 ◽

Author(s):

Alan Landay

Keyword(s):

Type I Interferon ◽

Type I ◽

Interferon Signaling ◽

Lcmv Infection

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Faculty Opinions recommendation of USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718217888.793499915 ◽

2014 ◽

Author(s):

Ganes Sen ◽

Saurabh Chattopadhyay

Keyword(s):

Type I Interferon ◽

Type I ◽

Interferon Signaling

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Identification of key mRNAs and lncRNAs involved in the effects of anti-TWEAK on Osteosarcoma

Current Bioinformatics ◽

10.2174/1574893615999200626191405 ◽

2020 ◽

Vol 15 ◽

Author(s):

Mingxuan Yang ◽

Liangtao Zhao ◽

Xuchang Hu ◽

Haijun Feng ◽

Xuewen Kang

Keyword(s):

Dna Replication ◽

Signaling Pathway ◽

Bioinformatics Analysis ◽

Mapk Signaling ◽

Migration And Invasion ◽

Type I ◽

Interferon Signaling ◽

Nf Kappa B ◽

Ppi Networks ◽

Coexpression Networks

Background: Osteosarcoma (OS) is one of the most common primary malignant bone tumors in teenagers. Emerging studies demonstrated TWEAK and Fn14 were involved in regulating cancer cell differentiation, proliferation, apoptosis, migration and invasion. Objective: The present study identified differently expressed mRNAs and lncRNAs after anti-TWEAK treatment in OS cells using GSE41828. Methods: We identified 922 up-regulated mRNAs, 863 downregulated mRNAs, 29 up-regulated lncRNAs, and 58 down-regulated lncRNAs after anti-TWEAK treatment in OS cells. By constructing PPI networks, we identified several key proteins involved in anti-TWEAK treatment in OS cells, including MYC, IL6, CD44, ITGAM, STAT1, CCL5, FN1, PTEN, SPP1, TOP2A, and NCAM1. By constructing lncRNAs coexpression networks, we identified several key lncRNAs, including LINC00623, LINC00944, PSMB8-AS1, LOC101929787. Result: Bioinformatics analysis revealed DEGs after anti-TWEAK treatment in OS were involved in regulating type I interferon signaling pathway, immune response related pathways, telomere organization, chromatin silencing at rDNA, and DNA replication. Bioinformatics analysis revealed differently expressed lncRNAs after antiTWEAK treatment in OS were related to telomere organization, protein heterotetramerization, DNA replication, response to hypoxia, TNF signaling pathway, PI3K-Akt signaling pathway, Focal adhesion, Apoptosis, NF-kappa B signaling pathway, MAPK signaling pathway, FoxO signaling pathway. Conclusion: : This study provided useful information for understanding the mechanisms of TWEAK underlying OS progression and identifying novel therapeutic markers for OS.

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