Mining database for the therapeutic targets and prognostic biomarkers among STAT family in glioblastoma

2020 ◽  
pp. 1-13
Author(s):  
Chenglin Li ◽  
Yanfei Zhou ◽  
Hanshun Deng ◽  
Yuanshen Ye ◽  
Shuizhen Zhao ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Web Applications ◽  
Therapeutic Targets ◽  
Prognostic Biomarkers ◽  
Receptor Interaction ◽  
Immune Gene ◽  
Nf Kappa B ◽  
Signal Transducers ◽  
Pathways Analysis

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with a high mortality rate. Aberrant activation of signal transducers and activators of transcription (STAT) signaling results in tumor pathogenesis and progression by regulating cell cycle, cell survival and immune response. METHODS: Therapeutic targets and prognostic biomarkers within the STAT family in GBM were explored using web applications and databases. RESULTS: High levels of STAT1/3/5A/5B/6 and low levels of STAT4 were observed in GBM patients. GBM patients expressing high STAT1/2/3/5A/6 and low STAT4/5B levels had the worse overall survival. Among the STAT family, STAT4 and STAT6 were the most frequently mutated genes. A low to moderate correlation among members of the STAT family was observed. Additionally, the STATs were involved in activation or inhibition of cancer related pathways. Analysis of immune infiltrates showed STAT5A levels to be significantly correlated with abundance of immune cells and levels of immune gene biomarkers. Gene ontology (GO) functions and KEGG pathway analysis indicated that STAT5A is involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway. Moreover, several kinase and transcription factor targets of STAT5A in GBM were identified. CONCLUSION: We report here therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM. These findings lay a foundation for further studies on the role of STAT family in therapy and prognosis of GBM. Further studies are required to verify our results.

scholarly journals Identification of therapeutic targets and prognostic biomarkers among STAT family in glioblastoma

2020 ◽  
Author(s):  
Chenglin Li ◽  
Yanfei Zhou ◽  
Hanshun Deng ◽  
Yuanshen Ye ◽  
Shuizhen Zhao ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Web Applications ◽  
Therapeutic Targets ◽  
Prognostic Biomarkers ◽  
Receptor Interaction ◽  
Immune Gene ◽  
Kegg Pathways ◽  
Incidence And Mortality ◽  
Regulation Network

Abstract Background: Glioblastoma (GBM) is the most common and aggressive primary brain malignancies with high incidence and mortality. The aberrant activation of STAT signaling was confirmed to result in tumor pathogenesis and progress by regulating cell cycle, cell survival, and immune response. Methods: The clinical significance of and regulation network of STAT family in GBM were explored with several web applications or database. Results: The level of STAT1/3/5A/5B/6 were increased in GBM while STAT4 level was decreased. GBM patients with high expression of STAT1/2/3/5A/6 and low expression of STAT4/5B had a worse overall survival. Among the STAT family, STAT 4 and STAT6 were the top two frequently mutated genes. Correlation suggested a low to moderate correlation among STAT family. STAT family were also involved in the activation or inhibition of the famous cancer related pathways. Immune infiltrates analysis suggested that STAT5A level showed significantly correlated with the abundance of immune cells and the level of immune gene biomarkers. GO functions and KEGG pathways analysis revealed that STAT5A was involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Moreover, we also identified several Kinase and transcription factor targets of STAT5A in GBM. Conclusions: Our results revealed the therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM, laying the foundation for further studies about STAT family in therapy and prognosis of GBM.

scholarly journals Identification of Prognostic Biomarkers and Immunotherapeutic Targets with CXC Chemokines in Glioblastoma Multiforme Using Integrated Bioinformatic Analysis

2020 ◽  
Author(s):  
Hailing Liu ◽  
Jinguang Zhu ◽  
Guangwen Wang
Keyword(s):  
Transcription Factors ◽  
Glioblastoma Multiforme ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Disease Free Survival ◽  
Bioinformatic Analysis ◽  
Differentially Expressed ◽  
Prognostic Biomarkers ◽  
Receptor Interaction ◽  
Dismal Prognosis

Abstract Background Glioblastoma multiforme (GBM) is the most malignant central nervous system tumour bearing a dismal prognosis. The study aimed to explore the potential biomarkers and therapeutic targets with CXC chemokines in GBM by integrated bioinformatics analysis.Methods Differentially expressed CXC Chemokines were identified in GBM using GEPIA and UALCAN databases,and Kaplan–Meier analyses were performed by GEPIA subsequently. Protein -protein interaction (PPI) network was established in STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to analyze differentially expressed CXC Chemokines and their similar genes gained from GEPIA. Then, we conducted transcription factors, kinase targets, and immune cells infiltration using TRRUST, LinkedOmics, and TIMER, respectively.Results The mRNA expression levels of CXCL3/5/6/9/10/11/12/13/16 in GMB were significantly elevated compared to normal tissues. GBM patients with higher transcriptional levels of CXCL5/6 were significantly associated with worse disease-free survival, while higher transcriptional levels of CXCL3/5/8 were significantly related to worse overall survival. The functions of CXC chemokines were enriched in Chemokine signaling pathway, Cytokine-cytokine receptor interaction, IL-17 signaling pathway, et.al. RELA and NFKB1were key transcription factors of CXC chemokines. The kinase targets of CXC chemokine contained CDK1, CDK2, PRKCD, MAPK14, ATM, LCK, MTOR, and GRK3, which are involved in oncogenesis, migration, and survival. Moreover, we revealed significant correlations between the expression of CXC chemokines and the infiltration immune cells, especially for dendritic cells.Conclusion The significant CXC chemokines and related pathways may provide a novel possibility for prognostic biomarkers and immunotherapeutic treatment in GMB.Short title: CXC Chemokines with prognosis in GBM

scholarly journals Clustering Analysis of Splenocyte MicroRNAs in Pig Reveals the Key Signal Regulators in Immune Modulation of the Host During the Acute and Chronic Toxoplasma Gondii Infection

2021 ◽  
Author(s):  
Zhaofeng Hou ◽  
Hui Zhang ◽  
Kangzhi Xu ◽  
Shifan Zhu ◽  
Lele Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Hierarchical Clustering ◽  
Immune Regulation ◽  
Clustering Analysis ◽  
Expression Patterns ◽  
Signaling Molecules ◽  
Receptor Interaction

Abstract Background: Toxoplasma gondii is an obligatory intracellular protozoan parasite that can cause a geographically widespread zoonosis. Our previous splenocyte microRNA profiles analyses of pig infected with T. gondii revealed that the coordination of a large number of miRNAs regulates the host immune response during infection. However, the functions of more miRNAs involved to the immune regulation during T. gondii infection are not yet known.Methods: Clustering analysis was performed by K-means, self-organizing map (SOM) and Hierarchical clustering, respectively, to obtain miRNA groups with the similar expression patterns. Then, the target genes of miRNA group in each subcluster were further analyzed for function enrichment by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway to recognize the key signaling molecules and the regulatory signatures of the innate and adaptive immune responses of the host during T. gondii infection.Results: A total of 252 miRNAs were successfully divided into 22 subclusters by K-means clustering (named by K1~K22), 29 subclusters by SOM clustering (named by SOM1~SOM29) and 6 subclusters by Hierarchical clustering (named by H1~H6) based on their dynamic expression levels in the different infection stages. A total of 634, 660 and 477 GO terms, 15, 26 and 14 KEGG pathways, and 16, 15 and 7 Reactome pathways were significantly enriched by K-means, SOM and Hierarchical clustering, respectively. Of note, up to 22 miRNAs mainly showing the downregulated expression at 50 DPI were identified into one subcluster (namely subcluster H3-K17-SOM1) through the three algorithms. Functional analysis revealed that a large group of immunomodulatory signaling molecules were controlled by the different miRNA groups to regulate multiple immune processes, for instance, IL-1-mediated cellular response and Th1/Th2 cell differentiation partly depending on Notch signaling transduction for subclusters K1 and K2, innate immune response involving to Neutrophil degranulation and TLR4 cascade signaling for subcluster K15, B cell activation for subclusters SOM17, SOM1 and SOM25, leukocyte migration and chemokine activity for subcluster SOM9, Cytokine-cytokine receptor interaction for subcluster H2, and interleukin production, chemotaxis of immune cells, Chemokine signaling pathway and C-type lectin receptor signaling pathway for subcluster H3-K17-SOM1.Conclusions: Clustering analysis of splenocyte microRNAs in pig reflected the key regulatory properties of subcluster miRNA molecules, as well as the important features in the immune regulation induced by acute and chronic infections of T. gondii. These results contribute to new insight into the identification of physiologic immune responses and maintenance of tolerance in pig spleen tissues during T. gondii infection.

Identification of key lncRNAs and mRNAs associated with Oral squamous cell carcinoma progression

2020 ◽  
Vol 15 ◽  
Author(s):  
Yong Mi ◽  
Na Li ◽  
Qing Li ◽  
Yang Shi ◽  
Congcong Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Type I ◽  
Catabolic Process

Background: Oral squamous cell carcinoma (OSCC) had been the sixth most common cancer worldwide. Emerging studies showed long non-coding RNAs played a key role in human cancers. However, the molecular mechanisms underlying the initiation and progression of OSCC remained to be further explored Objective: The present study aimed to identify differentially expressed lncRNAs and mRNAs in OSCC. Methods: GSE30784 was analyzed to identify differentially expressed lncRNAs and mRNAs in OSCC. Protein-protein interaction network and co-expression network analysis were performed to reveal the potential roles of OSCC related mRNAs and lncRNAs Results: In present study, we identified 21 up-regulated lncRNAs and 54 down-regulated lncRNAs in OSCC progression. Next we constructed a lncRNA related co-expression network in OSCC, which included 692 mRNAs and 2193 edges. Bioinformatics analysis showed lncRNAs were widely co-expressing with regulating type I interferon signaling pathway, extracellular matrix organization, collagen catabolic process, immune response, ECM-receptor interaction, Focal adhesion, and PI3K-Akt signaling pathway. A key network, included lncRNA C5orf66-AS1, C21orf15, LOC100506098, PCBP1-AS1, LOC284825, OR7E14P, HCG22, and FLG-AS1, were found to be involved in the regulation of immune response to tumor cell, Golgi calcium ion transport, negative regulation of vitamin D receptor signaling pathway, glycerol-3-phosphate catabolic process. Moreover, we found showed higher expression of CYP4F29P, PCBP1-AS1, HCG22, and C5orf66-AS1were associated with shorter overall survival time in OSCC samples Conclusions: We thought our analysis could provide novel insights to explore the potential mechanisms underlying OSCC progression

scholarly journals Comprehensive Analysis of Immunoinhibitors Identifies LGALS9 and TGFBR1 as Potential Prognostic Biomarkers for Pancreatic Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yue Fan ◽  
Tianyu Li ◽  
Lili Xu ◽  
Tiantao Kuang
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Expression Patterns ◽  
Prognostic Biomarkers ◽  
Type I ◽  
Hippo Signaling ◽  
Nf Kappa B ◽  
Aberrant Expression ◽  
Wide Range ◽  
Molecular Therapeutic

Pancreatic cancer (PC) is one of the most deadly cancers worldwide. To uncover the unknown novel biomarker used to indicate early diagnosis and prognosis in the molecular therapeutic field of PC is extremely of importance. Accumulative evidences indicated that aberrant expression or activation of immunoinhibitors is a common phenomenon in malignances, and significant associations have been noted between immunoinhibitors and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of immunoinhibitors contributing to tumorigenesis and progression of pancreatic cancer (PC) have not yet been elucidated clearly. In this study, we investigated the distinct expression and prognostic value of immunoinhibitors in patients with PC by analyzing a series of databases, including TISIDB, GEPIA, cBioPortal, and Kaplan-Meier plotter database. The mRNA expression levels of IDO1, CSF1R, VTCN1, KDR, LGALS9, TGFBR1, TGFB1, IL10RB, and PVRL2 were found to be significantly upregulated in patients with PC. Aberrant expression of TGFBR1, VTCN1, and LGALS9 was found to be associated with the worse outcomes of patients with PC. Bioinformatics analysis demonstrated that LGALS9 was involved in regulating the type I interferon signaling pathway, interferon-gamma-mediated signaling pathway, RIG-I-like receptor signaling pathway, NF-kappa B signaling pathway, cytosolic DNA-sensing pathway, and TNF signaling pathway. And TGFB1 was related to mesoderm formation, cell matrix adhesion, TGF-beta signaling pathway, and Hippo signaling pathway. These results suggested that LGALS9 and TGFBR1 might serve as potential prognostic biomarkers and targets for PC.

scholarly journals SUMOylation of GMFB regulates the stability and function of GMFB in RPE cells under oxidative stress and inflammation

2021 ◽  
Author(s):  
Wan Sun ◽  
Juan Wang ◽  
Jieping Zhang ◽  
Furong Gao ◽  
Qingjian Ou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Age Related Macular Degeneration ◽  
Receptor Interaction ◽  
Receptor Signaling ◽  
Post Translational Modification ◽  
Nf Kappa B ◽  
Age Related ◽  
Receptor Signaling Pathway ◽  
And Function

AbstractGlia maturation factor beta (GMFB) is a growth and differentiation factor that act as an intracellular regulator of signal transduction pathways. The SUMOylation is a post-translational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. But little is known about the relationship between GMFB and SUMOylation. Here we first report that GMFB can be mono-SUMOylated at multiple sites by the covalent addition of a single SUMO1 protein, and identified K20, K35, K58, and K97 as major SUMO acceptor sites. We also found that SUMOylation leading to increased stability and trans-localization of GMFB. Furthermore, RNA-seq data and Real-time quantitative polymerase chain reaction (rt-qPCR) also indicated that the SUMOylated GMFB upregulated multiple pathways, including the cytokine-cytokin receptor interaction, NOD-like receptor signaling pathway, TNF signaling pathway, RIG-I-like receptor signaling pathway, and NF-kappa B signaling pathway. Our studies intend to provide a novel direction for the study into the biofunction of GMFB, SUMOylated GMFB and the mechanism, clinical therapy, and prognosis of inflammation-related RPE disorders like age-related macular degeneration (AMD) and diabetic retinopathy (DR).

scholarly journals Integrative Omics Analysis Reveals the Immunomodulatory Effects of the Parasitic Dinoflagellate Hematodinium on Crustacean Immunity

2021 ◽  
Author(s):  
Meng Li ◽  
Qian Huang ◽  
Xiaoyang Lv ◽  
Hamish J. Small ◽  
Caiwen Li
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Host Immune Response ◽  
Portunus Trituberculatus ◽  
Economic Losses ◽  
Receptor Interaction ◽  
Host Immune Responses ◽  
Humoral Immune ◽  
Host Parasite ◽  
Post Transcriptional Regulation

Parasitic dinoflagellates in genus Hematodinium have caused substantial economic losses to multiple commercially valuable marine crustaceans around the world. In the present study, comprehensive omics approaches (miRNA transcriptomics, iTRAQ-based proteomics) were applied to investigate the host-parasite interaction between hemocytes from Portunus trituberculatus and Hematodinium perezi. The parasitic dinoflagellate remodeled the miRNome and proteome of hemocytes from challenged hosts, modulated the host immune response at both post-transcriptional and translational levels and caused post-transcriptional regulation to the host immune response. Multiple important cellular and humoral immune-related pathways (ex. Apoptosis, Endocytosis, ECM-receptor interaction, proPO activation pathway, Toll-like signaling pathway, Jak-STAT signaling pathway) were significantly affected by Hematodinium parasites. Through modulation of the host miRNome, the host immune responses of nodulation, proPO activation and antimicrobial peptides were significantly suppressed. Cellular homeostasis was imbalanced via post-transcriptional dysregulation of the phagosome, peroxisome, and lysosome pathways. Cellular structure and communication was seriously impacted by post-transcriptional downregulation of ECM-receptor interaction and focal adhesion pathways.

scholarly journals Ginseng Stem-Leaf Saponins in Combination with Selenium Promote the Immune Response in Neonatal Mice with Maternal Antibody

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 755
Author(s):  
Yong Wang ◽  
Lijia Yuan ◽  
Xuemei Cui ◽  
Wei Xu ◽  
Sijia Fang ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathway ◽  
Pseudorabies Virus ◽  
Killer Cell ◽  
Innate Immune ◽  
Maternal Antibody ◽  
Receptor Interaction ◽  
Adjuvant Effect ◽  
Neonatal Mice ◽  
Stem Leaf

Neonates acquire from their mothers maternal antibody (MatAb) which results in poor immune response to vaccination. We previously demonstrated that ginseng stem-leaf saponins in combination with selenium (GSe) had adjuvant effect on the immune response to an attenuated pseudorabies virus (aPrV) vaccine. The present study was to evaluate GSe for its effect on the immune response to aPrV vaccine in neonatal mice with MatAb. Results showed that GSe had adjuvant effect on the immune response to aPrV vaccine in neonates. When GSe was co-administered with aPrV vaccine (aP-GSe), specific gB antibody, Th1 cytokines (IL-2, IL-12 and IFN-γ) and Th2 cytokines (IL-4, IL-6 and IL-10) responses were significantly increased in association with enhanced protection of vaccinated neonates against the lethal PrV challenge even though MatAb existed when compared to the neonates immunized with aPrV vaccine alone. GSe-enhanced immune response depended on its use in the primary immunization. The mechanisms underlying the adjuvant effect of GSe may be due to more innate immune related pathways activated by GSe. Transcriptome analysis of splenocytes from neonates immunized with aP-GSe, aPrV or saline solution showed that there were 3976 differentially expressed genes (DEGs) in aP-GSe group while 5959 DEGs in aPrV group when compared to the control. Gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis showed that innate immune responses and cytokine productions related terms or pathways were predominantly enriched in aP-GSe group, such as “NOD-like receptor signaling pathway”, “Natural killer cell mediated cytotoxicity”, “NF-κB signaling pathway”, “cytokine-cytokine receptor interaction”, and “Th1 and Th2 cell differentiation”. Considering the potent adjuvant effect of GSe on aPrV vaccine in neonatal mice with MatAb, it deserves further investigation in piglets.

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