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.

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 RNA Sequencing (RNA-Seq) Based Transcriptome Analysis in Immune Response of Holstein Cattle to Killed Vaccine against Bovine Viral Diarrhea Virus Type I

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 344 ◽  
Author(s):  
Bryan Irvine Lopez ◽  
Kier Gumangan Santiago ◽  
Donghui Lee ◽  
Seungmin Ha ◽  
Kangseok Seo
Keyword(s):  
Immune Response ◽  
Enrichment Analysis ◽  
Receptor Interaction ◽  
Type I ◽  
Rna Seq ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Kegg Pathways ◽  
Viral Diarrhea Virus

Immune response of 107 vaccinated Holstein cattle was initially obtained prior to the ELISA test. Five cattle with high and low bovine viral diarrhea virus (BVDV) type I antibody were identified as the final experimental animals. Blood samples from these animals were then utilized to determine significant differentially expressed genes (DEGs) using the RNA-seq transcriptome analysis and enrichment analysis. Our analysis identified 261 DEGs in cattle identified as experimental animals. Functional enrichment analysis in gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed the DEGs potentially induced by the inactivated BVDV type I vaccine, and might be responsible for the host immune responses. Our findings suggested that inactivated vaccine induced upregulation of genes involved in different GO annotations, including antigen processing and presentation of peptide antigen (via MHC class I), immune response, and positive regulation of interferon-gamma production. The observed downregulation of other genes involved in immune response might be due to inhibition of toll-like receptors (TLRs) by the upregulation of the Bcl-3 gene. Meanwhile, the result of KEGG pathways revealed that the majority of DEGs were upregulated and enriched to different pathways, including cytokine-cytokine receptor interaction, platelet activation, extracellular matrix (ECM) receptor interaction, hematopoietic cell lineage, and ATP-binding cassette (ABC) transporters. These significant pathways supported our initial findings and are known to play a vital role in shaping adaptive immunity against BVDV type 1. In addition, type 1 diabetes mellitus pathways tended to be significantly enriched. Thus, further studies are needed to investigate the prevalence of type 1 diabetes mellitus in cattle vaccinated with inactivated and live BVDV vaccine.

scholarly journals Identification and analysis of small nucleolar RNAs (snoRNAs) associated co-expression and ceRNA regulatory networks in esophageal carcinoma

2020 ◽  
Author(s):  
Haigen Jiang ◽  
Jing Zhuang ◽  
Xi Yang ◽  
Wei Wu ◽  
Siqi Dai ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Esophageal Carcinoma ◽  
Trend Analysis ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Receptor Interaction ◽  
Small Nucleolar Rnas ◽  
Regulation Network ◽  
Nucleolar Rnas ◽  
Normal Controls

Abstract Background: This study aimed to investigate the role of small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) in tumorigenesis and progression of esophageal carcinoma (EC). Methods: RNA-seq data and clinical information for EC patients were obtained from The Cancer Genome Atlas database. Differentially expressed snoRNAs (DE-snoRNAs) and SNHGs (DE-SNHGs) between EC samples and normal controls were screened with the edgeR package, followed by the trend analysis with STEM. Survival analysis was performed using the Kaplan–Meier method with the log-rank test. Identification of co-expressed genes and functional enrichment analyses were performed with Pearson’s correlation analysis and enrichment analysis, respectively. Lastly, the co-expression and ceRNA networks were constructed. Results: A total of 19 DE-snoRNAs and nine DE-SNHGs were identified between EC samples and normal controls. Moreover, two snoRNA clusters related to the clinic stage were identified through trend analysis. Survival analysis results demonstrated that SNORA70D was significantly associated with the overall survival of EC patients (P=0.034). In addition, a co-regulation network that included six snoRNAs and 29 mRNAs was constructed. A ceRNA network comprised of five SNHGs, 11 mRNAs, and 38 miRNAs was constructed based on the top 50 relationship pairs. KEGG pathway enrichment analysis revealed that SNORA14B, SNORA47, SNORA71C, SNORD12B, and SNORD14E in the co-expression network were mainly enriched in the NOD−like receptor signaling pathway, and neuroactive ligand−receptor interaction pathway. SNHG23, SNHG3, SNHG17, SNHG4, and SNHG8 in the ceRNA regulation network were mainly enriched in calcium signaling pathway, cytokine−cytokine receptor interaction, and the extracellular matrix−receptor interaction pathway. Conclusion: The data revealed a series of snoRNAs, SNHGs, and pathways involved in EC carcinogenesis, which will provide a basis for understanding the underlying molecular mechanism of EC development.

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 Post-Translational Protein Deimination Signatures in Plasma and Plasma EVs of Reindeer (Rangifer tarandus)

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 222
Author(s):  
Stefania D’Alessio ◽  
Stefanía Thorgeirsdóttir ◽  
Igor Kraev ◽  
Karl Skírnisson ◽  
Sigrun Lange
Keyword(s):  
Signaling Pathway ◽  
Prion Disease ◽  
Rangifer Tarandus ◽  
Extreme Environments ◽  
Estrogen Signaling ◽  
The Arctic ◽  
Receptor Interaction ◽  
Wild Female ◽  
Hormone Synthesis ◽  
Kegg Pathways

The reindeer (caribou) Rangifer tarandus is a Cervidae in the order Artiodactyla. Reindeer are sedentary and migratory populations with circumpolar distribution in the Arctic, Northern Europe, Siberia and North America. Reindeer are an important wild and domesticated species, and have developed various adaptive strategies to extreme environments. Importantly, deer have also been identified to be putative zoonotic carriers, including for parasites, prions and coronavirus. Therefore, novel insights into immune-related markers are of considerable interest. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination by converting arginine into citrulline in target proteins. This affects protein function in health and disease. Extracellular vesicles (EVs) participate in cellular communication, in physiological and pathological processes, via transfer of cargo material, and their release is partly regulated by PADs. This study assessed deiminated protein and EV profile signatures in plasma from sixteen healthy wild female reindeer, collected in Iceland during screening for parasites and chronic wasting disease. Reindeer plasma EV profiles showed a poly-dispersed distribution from 30 to 400 nm and were positive for phylogenetically conserved EV-specific markers. Deiminated proteins were isolated from whole plasma and plasma EVs, identified by proteomic analysis and protein interaction networks assessed by KEGG and GO analysis. This revealed a large number of deimination-enriched pathways for immunity and metabolism, with some differences between whole plasma and EVs. While shared KEGG pathways for whole plasma and plasma EVs included complement and coagulation pathways, KEGG pathways specific for EVs were for protein digestion and absorption, platelet activation, amoebiasis, the AGE–RAGE signaling pathway in diabetic complications, ECM receptor interaction, the relaxin signaling pathway and the estrogen signaling pathway. KEGG pathways specific for whole plasma were pertussis, ferroptosis, SLE, thyroid hormone synthesis, phagosome, Staphylococcus aureus infection, vitamin digestion and absorption, and prion disease. Further differences were also found between molecular function and biological processes GO pathways when comparing functional STRING networks for deiminated proteins in EVs, compared with deiminated proteins in whole plasma. This study highlights deiminated proteins and EVs as candidate biomarkers for reindeer health and may provide information on regulation of immune pathways in physiological and pathological processes, including neurodegenerative (prion) disease and zoonosis.

scholarly journals The Identified Hub Gene GlcN in Osteoarthritis Progression and Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jingsheng Liu ◽  
Xiaoli Dong ◽  
Yining Liu ◽  
Kai Wang ◽  
Shuanhu Lei ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Point Of View ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Hub Genes ◽  
Data Set ◽  
Treatment Groups ◽  
R Language ◽  
Kegg Pathways ◽  
Osteoarthritis Progression

Background. As a chronic disease, osteoarthritis has caused great trouble to the health of middle-aged and elderly people. Studies have shown that glucosamine (GlcN) can be used to abate the progression and improve this disease. Based on this point of view, we try to verify the connection between GlcN and osteoarthritis and find more effective biomarkers. Methods. We downloaded the GSE72575 data set from the GEO database, and used the R language to perform DEG analysis on the gene expression profile of the samples. Next, the GO function and the KEGG signaling pathways were analyzed through the DAVID database, and then, the KEGG pathways enriched in the gene set were analyzed based on GSEA. Then, the PPI network of DEGs was constructed based on the STRING online database, and finally, the hub genes were selected by Cytoscape. Results. Three GlcN-treated MH7A cell treatment groups and 3 control groups in the GSE72575 data set were studied. Through analysis, there were 52 DEGs in these samples. Then, through GO, KEGG, and GSEA, regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway, FoxO signaling pathway, JAK-STAT signaling pathway, PI3K-Akt signaling pathway, TGF-beta signaling pathway, and ECM receptor interaction were involved in the regulatory mechanisms of the osteoarthritis pathogenesis. After that, the hub genes IL6 and DDIT3 were identified through PPI network construction and analysis. And it was found that IL6 was lowly expressed in the group with GlcN-treated MH7A cells, while DDIT3 was highly expressed. Conclusion. The above results provide a basis for GlcN to participate in the treatment of osteoarthritis and a possibility for finding effective therapeutic targets.

scholarly journals Cartilage Targets of Knee Osteoarthritis Shared by Both Genders

2021 ◽  
Vol 22 (2) ◽  
pp. 569
Author(s):  
Chenshuang Li ◽  
Zhong Zheng
Keyword(s):  
Signaling Pathway ◽  
Current Knowledge ◽  
Receptor Interaction ◽  
Akt Signaling Pathway ◽  
Cell Plasma Membrane ◽  
Kegg Pathways ◽  
Papillomavirus Infection ◽  
Cell Plasma ◽  
Males And Females ◽  
Gender Specific

As the leading cause of disability, osteoarthritis (OA) affects people of all ages, sexes, and races. With the increasing understanding of OA, the sex differences have attracted specific attention as the burden of OA is greater in women. There is no doubt that gender-specific OA management has great potential for precision treatment. On the other hand, from the marketing aspect, a medication targeting the OA-responsive biomarker(s) shared by both genders is more favorable for drug development. Thus, in the current study, a published transcriptome dataset of knee articular cartilage was used to compare OA and healthy samples for identifying the genes with the same significantly different expression trend in both males and females. With 128 genes upregulated and 143 genes downregulated in both OA males and females, 9 KEGG pathways have been enriched based on the current knowledge, including ‘renal cell carcinoma,’ ‘ECM-receptor interaction,’ ‘HIF-1 signaling pathway,’ ‘MicroRNAs in cancer,’ ‘focal adhesion,’ ‘Relaxin signaling pathway,’ ‘breast cancer,’ ‘PI3K-Akt signaling pathway,’ and ‘human papillomavirus infection.’ Here, we explore the potential impacts of these clusters in OA. We also analyze the identified ‘cell plasma membrane related genes’ in-depth to identify the potential chondrocyte cell surface target(s) of OA management.

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