ISG12a inhibits HCV replication and potentiates the anti-HCV activity of IFN-α through activation of the Jak/STAT signaling pathway independent of autophagy and apoptosis

Chen, Yanzhao; Jiao, Baihai; Yao, Ming; Shi, Xuezhen; Zheng, Zhe-Bin; Li, Shilin; Chen, Limin

doi:10.1016/j.virusres.2016.10.013

Cited by 39 publications

(26 citation statements)

References 32 publications

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“…IFI27 is a member of the interferon alpha inducible proteins that may participate in the pathogenesis of various viral infections (23). IFI27 was con rmed to be involved in a series of biological pathways: innate immune, interferon gamma signaling, RNA polymerase II activating transcription factor binding and lamin binding (24).…”

Section: Discussionmentioning

confidence: 99%

IFI27 May Predict and Evaluate the Severity of Respiratory Syncytial Virus Infection in Preterm Infants

Gao

Zhu

et al. 2020

Preprint

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Background: Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infection (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection. Methods: Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein‐protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out. Results: Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p=0.041), more requirements of mechanical ventilation (p=0.034), more frequent hospitalization (p<0.001) and longer cumulative hospital stay (p=0.012). Conclusion: IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.

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Section: Discussionmentioning

confidence: 99%

IFI27 May Predict and Evaluate the Severity of Respiratory Syncytial Virus Infection in Preterm Infants

Gao

Zhu

et al. 2020

Preprint

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“…Furthermore, ISG12a is another ISG family member that promotes the production of IFN α/β and activates the type I IFN signaling pathway as shown by increasing p-STAT1 levels, up-regulating ISG levels and elevating Interferon sensitive response element (ISRE) activity. ISG12a can inhibit the replication of HCV and promote the anti-HCV activity of IFN-α probably by the production of type I IFNs and activation of Jak/STAT signaling pathway [112]. …”

Section: Introductionmentioning

confidence: 99%

The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells

et al. 2017

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The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed.

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“…Rather, IL-17 signals through nuclear factor (NF)-κB (13), mitogen-activated protein kinase (MAPK) (14) and phosphoinositide 3-kinase (PI3K) (14) signaling pathways. The janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays an important role in regulating a number of pathways associated with tumorigenesis, including cell cycle progression, apoptosis and tumor cell evasion of the immune system (15,16). In a previous study, phosphorylation of STAT3 was markedly increased as early as 3 h following IL-17 treatment and lasted for 24 h (17), which indicated that JAK2/STAT3 signaling may have important roles in tumor progression associated with IL-17.…”

Section: Introductionmentioning

confidence: 99%

Autophagy impacts on oxaliplatin-induced hepatocarcinoma apoptosis via the IL-17/IL-17R-JAK2/STAT3 signaling pathway

Guo

Cao

et al. 2016

Oncology Letters

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Abstract. The interleukin (IL)-17/IL-17 receptor (IL-17R)complex has been shown to be important for the regulation of inflammation; however, its role in the regulation of tumor processes has recently emerged as a research focus. The present study demonstrated that oxaliplatin was able to increase the levels of IL-17/IL-17R in hepatocellular carcinoma (HCC) patients and cells lines, and that it had important roles in reducing the susceptibility of the cells to oxaliplatin-induced apoptosis. Furthermore, the expression of autophagy-related proteins was induced by IL-17/IL-17R and autophagy was shown to induce resistance to oxaliplatin in HCC. In addition, the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was shown to be an important pathway in the induction of autophagy in response to oxaliplatin. Autopjhagy was inhibited by 3-methyladenine and JAK2/STAT3 signaling was blocked by AG490, which induced apoptosis in SMMC7721 cells treated with oxaliplatin. The results of the present study may help to elucidate the mechanism underlying the role of IL-17/IL-17R-induced autophagy in the chemoresistance of HCC, as well as help to establish and develop measures to overcome chemoresistance in HCC. IntroductionHepatocellular carcinoma (HCC) is a major malignancy worldwide and its incidence is increasing annually; it is the second most common cause of cancer-associated mortality (1).The majority of patients have a low survival rate as a result of locally advanced or metastatic diseases, and surgery is feasible for only a small percentage of patients with HCC. Therefore, chemotherapy is the optimal therapeutic strategy for inoperable HCC (2). Oxaliplatin has been widely used in chemotherapy to reduce tumor recurrence and prolong survival in patients with HCC because of its fewer side effects compared with other platinum drugs (3). However, chemoresistance to oxaliplatin in the form of suppressed HCC apoptosis is commonly observed (4).Interleukin-17 (IL-17) is predominantly secreted by interleukin-17-producing T-helper (Th17) cells, which participate in the progression and pathogenesis of inflammatory diseases (3). The IL-17 receptor (IL-17R) is expressed on the surface of numerous cells, including macrophages, dendritic cells, epithelial cells, fibroblasts and T lymphocytes (5,6). Previous studies reported that IL-17-producing cells accumulated in tumors (7,8), and that patients with malignant serum effusions (9) or multiple myeloma (10) showed significantly higher serum levels of IL-17. Furthermore, patients with persistently higher levels of IL-17 demonstrated the requirement for longer courses of chemotherapy, since these patients comprised a significant proportion of all cases of recurrence (11). Typically, IL-17 does not engage with Toll/IL-1 receptor (TIR) domain-containing adaptors, such as MyD88, TIR domain-containing adapter protein inducing interferon-β or IL-1 receptor-associated kinases (12). Rather, IL-17 signals through nuclear factor (NF)-κB (13), mitogen-activated pro...

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ISG12a inhibits HCV replication and potentiates the anti-HCV activity of IFN-α through activation of the Jak/STAT signaling pathway independent of autophagy and apoptosis

Cited by 39 publications

References 32 publications

IFI27 May Predict and Evaluate the Severity of Respiratory Syncytial Virus Infection in Preterm Infants

IFI27 May Predict and Evaluate the Severity of Respiratory Syncytial Virus Infection in Preterm Infants

The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells

Autophagy impacts on oxaliplatin-induced hepatocarcinoma apoptosis via the IL-17/IL-17R-JAK2/STAT3 signaling pathway

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