scholarly journals Identification of hub genes and pathways in psoriasis through bioinformatics and validation by RT-qPCR

2021 ◽  
Author(s):  
Ling Ai Zou ◽  
Qichao Jian
Keyword(s):  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
Hacat Cells ◽  
Receptor Signaling ◽  
Ppi Network ◽  
Hub Genes ◽  
Network Analyses ◽  
Receptor Signaling Pathway

Abstract Background Although several studies have attempted to investigate the aetiology and mechanism of psoriasis, the precise molecular mechanism remains unclear. Our study aimed to identify the hub genes and associated pathways that promote its pathogenesis in psoriasis, which would be helpful for the discovery of diagnostic and therapeutic markers. Methods GSE30999, GSE34248, GSE41662, and GSE50790 datasets were extracted from the Gene Expression Omnibus (GEO) database. The GEO profiles were integrated to obtain differentially expressed genes (DEGs) using the affy package in R software, with |logFC|> 1.5 and adjusted P < 0.05. The DEGs were utilised for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network analyses. Hub genes were identified using Cytoscape and enriched for analysis in www.bioinformatics.com.cn. These hub genes were validated in the four aforementioned datasets and M5-induced HaCaT cells using real-time quantitative polymerase chain reaction (RT-qPCR). Results A total of 359 DEGs were identified, which were mostly associated with responses to bacterium, defence responses to other organism, and antimicrobial humoral response. These DEGs were mostly enriched in the steroid hormone biosynthesis pathway, NOD-like receptor signaling pathway, and cytokine-cytokine receptor interaction. PPI network analysis indicated seven genes (CXCL1, ISG15, CXCL10, STAT1, OASL, IFIT1, and IFIT3) as the probable hub genes of psoriasis; CXCL10 had a positive correlation with the other six hub genes. The chord plot results further supported the GO and KEGG analysis results of the 359 DEGs. Seven predicted hub genes were validated to be upregulated in four datasets and M5-induced HaCaT cells using RT-qPCR. Conclusions The pathogenesis of psoriasis may be associated with seven hub genes (CXCL1, ISG15, CXCL10, STAT1, OASL, IFIT1, and IFIT3) and pathways, such as the NOD-like receptor signaling pathway and cytokine-cytokine receptor interaction. These hub genes, especially CXCL10, can be used as potential biomarkers in psoriasis.

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 Diagnostic Value of DHX58 - IRF7 Involved in RIG-I-Like Receptor Signaling Pathway in Tuberculosis

2021 ◽  
Author(s):  
Chong-hui Li ◽  
Yu-rong Fu ◽  
zhengjun yi
Keyword(s):  
Dendritic Cell ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Diagnostic Value ◽  
Receptor Interaction ◽  
Receptor Signaling ◽  
Hub Genes ◽  
Roc Curve Analysis ◽  
Diagnostic Efficacy ◽  
Receptor Signaling Pathway

Abstract Background: Tuberculosis (TB) is an infectious disease that endangers human health. This study set out to search for key genes and related pathways in dendritic cell (DC) from TB patients to reveal the potential molecular mechanisms and identify potential biomarkers for TB.Method: DC data GSE34151 related to TB was downloaded from GEO data sets for analysis. Differentially expressed genes (DEGs) were obtained by employing an online tool, GEO2R. PPI network of DEGs and gene module were visualized and calculated applying STRING and Cytoscape, respectively. GO analysis and KEGG pathway were utilized to annotate the functions of DEGs. ROC curve analysis was applied to screen the most diagnostic hub genes associated with TB. Furthermore, their expression was validated in blood data (GSE83456), which were further compared to the T-spot·TB test.Results: A total of 290 DEGs were screened, which were significantly enriched in Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, and RIG-I-like receptor signaling pathways. Among them, 27 candidate hub genes with the most significant cluster in PPI were enriched in RIG-I-like receptor signaling pathway, which has been known to be associated with TB. We further found that the top 10 hub genes(DHX58, ISG20, IRF1, IRF7 and RSAD2, etc) showed high performance for TB diagnosis, among which both DHX58 and IRF7 were enriched in the RIG-I-like receptor signaling pathway. Moreover, DHX58 and IRF7 were also increased in blood, which were consistent with that in dendritic cell. Interestingly, DHX58 and IRF7 display higher diagnostic efficacy than T-spot·TB test.Conclusion: In this study, we revealed that both DHX58 and IRF7 with high diagnostic value in blood and dendritic cells, potentially involved in RIG-I-like receptor signaling pathway, may serve as a marker for TB diagnosis.

scholarly journals Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zongfu Pan ◽  
Lu Li ◽  
Qilu Fang ◽  
Yangyang Qian ◽  
Yiwen Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Signaling Pathway ◽  
Regulatory Network ◽  
Anaplastic Thyroid Carcinoma ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Hub Genes ◽  
Normal Thyroid ◽  
Master Regulators

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapidly lethal tumors. However, limited advances have been made to prolong the survival and to reduce the mortality over the last decades. Therefore, identifying the master regulators underlying ATC progression is desperately needed. In our present study, three datasets including GSE33630, GSE29265, and GSE65144 were retrieved from Gene Expression Omnibus with a total of 32 ATC samples and 78 normal thyroid tissues. A total of 1804 consistently changed differentially expressed genes (DEGs) were identified from three datasets. KEGG pathways enrichment suggested that upregulated DEGs were mainly enriched in ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, focal adhesion, and p53 signaling pathway. Furthermore, key gene modules in PPI network were identified by Cytoscape plugin MCODE and they were mainly associated with DNA replication, cell cycle process, collagen fibril organization, and regulation of leukocyte migration. Additionally, TOP2A, CDK1, CCNB1, VEGFA, BIRC5, MAPK1, CCNA2, MAD2L1, CDC20, and BUB1 were identified as hub genes of the PPI network. Interestingly, module analysis showed that 8 out of 10 hub genes participated in Module 1 network and more than 70% genes of Module 2 consisted of collagen family members. Notably, transcription factors (TFs) regulatory network analysis indicated that E2F7, FOXM1, and NFYB were master regulators of Module 1, while CREB3L1 was the master regulator of Module 2. Experimental validation showed that CREB3L1, E2F7, and FOXM1 were significantly upregulated in ATC tissue and cell line when compared with normal thyroid group. In conclusion, the TFs regulatory network provided a more detail molecular mechanism underlying ATC occurrence and progression. TFs including E2F7, FOXM1, CREB3L1, and NFYB were likely to be master regulators of ATC progression, suggesting their potential role as molecular therapeutic targets in ATC treatment.

scholarly journals Integrated Bioinformatic Analysis of Key Biomarkers and Signaling Pathways in Psoriasis

2021 ◽  
Author(s):  
Suwei Tang ◽  
Ping Xu ◽  
Shaoqiong Xie ◽  
Wencheng Jiang ◽  
Jiajing Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Immune Cell ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Hub Genes ◽  
Diagnostic Efficacy ◽  
Network Analyses

Abstract Background: Psoriasis is a relatively common autoimmune inflammatory skin disease with a chronic etiology. The present study was designed to detect novel biomarkers and pathways associated with psoriasis incidence. Methods: Differentially expressed genes (DEGs) associated with psoriasis in the Gene Expression Omnibus (GEO) database were identified, and their functional roles and interactions were then annotated and evaluated through GO, KEGG, and gene set variation (GSVA) analyses. In addition, the STRING database was leveraged to construct a protein-protein interaction (PPI) network, and key hub genes from this network were validated as being relevant through receiver operating characteristic (ROC) curve analyses of three additional GEO datasets. The CIBERSORT database was additionally used to assess the relationship between these gene expression-related findings and immune cell infiltration. Results: In total 197 psoriasis-related DEGs were identified and found to primarily be associated with the NOD-like receptor, IL-17, and cytokine-cytokine receptor interaction signaling pathways. GSVA revealed significant differences between normal and lesional groups (P < 0.05), while PPI network analyses identified CXCL10 as the hub gene with the highest degree value, whereas IRF7, IFIT3, OAS1, GBP1, and ISG15 were promising candidate genes for the therapeutic treatment of psoriasis. ROC analyses confirmed that these 6 hub genes exhibited good diagnostic efficacy (AUC > 70%), and were predicted to be associated with increased sensitivity to 10 drugs (P < 0.01). The CIBERSORT database further predicted that these hub genes were associated with infiltration by 22 different immune cell types. Conclusion: These results offer a robust foundation for future studies of the molecular basis for psoriasis, potentially guiding efforts to treat this common and disruptive disease.

scholarly journals PF168 KINASE AND CYTOKINE RECEPTOR SIGNALING PATHWAY ACTIVATING ALTERATIONS IN UNIFORMLY TREATED B-ALL

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 36
Author(s):  
R. Norvilas ◽  
V. Dirsė ◽  
R. Sema-kevičienė ◽  
O. Mickevičiūtė ◽  
G. Vaitkevičienė ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cytokine Receptor ◽  
Receptor Signaling ◽  
Receptor Signaling Pathway

scholarly journals Analysis of transcriptomic changes in bovine endometrial stromal cells treated with lipopolysaccharide

2020 ◽  
Author(s):  
Xuefen Ding ◽  
Haimiao Lv ◽  
Lixin Deng ◽  
Wenju Hu ◽  
Zhan Peng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Stromal Cells ◽  
Interleukin 12 ◽  
Receptor Interaction ◽  
Control Group ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
Endometrial Stromal Cells ◽  
Receptor Signaling Pathway

Abstract Background: Endometritis adversely affects the ability of cattle to reproduce, and significantly reduces milk production. Consequently, it has great influence on the economic value of dairy cows. The endometrium is mainly composed of epithelial and stromal cells and they produce the first immune response to invading pathogens. Epithelial cells are the first cellular barrier through which bacteria enter the uterine endometrium. However, most of the epithelial cells are disrupted and stromal cells are exposed to an inflammatory environment when endometritis occurs, especially postpartum. A loss of the protective epithelium allows bacteria or toxins to access the underlying stromal cells. The activation of Toll-like receptor（TLRs）on stromal cells induces increased production of cytokines and chemokines. Understanding the genome-wide characterization of the bovine endometritis will be beneficial for prevention and treatment of endometritis. In this study, whole-transcriptomic gene changes in bovine stromal cells treated with LPS were compared with those treated with PBS (control group) and were analyzed by RNA sequencing (RNA-seq). Results: Compared with the control group, a total of 366 differentially expressed genes (DEGs) were identified in LPS-induced group (234 upregulated and 132 downregulated genes), with an adjusted P-value＜0.05 by DESeq. Gene ontology (GO) enrichment analysis revealed DEGs were most enriched in lymphocyte activation, interleukin-1 receptor binding, regulation of cell activation, and lymphocyte-activated interleukin-12 production. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed DEGs were most enriched in TNF signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, nucleotide-binding oligomerization domain-like (NOD-like) receptor signaling pathway, NF-κB signaling pathway, and chemokine signaling pathway.Conclusion: The results of this study unraveled endometrial stromal cells transcriptome profile alterations in bovine affected by LPS which may have a significant effect on the eliminating or reducing inflammation by comprehending molecular mechanisms and authenticating unique genes related to endometritis.

scholarly journals Screening of Hub Genes Associated with Pulmonary Arterial Hypertension by Integrated Bioinformatic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yu Zeng ◽  
Nanhong Li ◽  
Zhenzhen Zheng ◽  
Riken Chen ◽  
Min Peng ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Drug Targets ◽  
Bioinformatic Analysis ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Hub Genes ◽  
Network Analyses ◽  
Pulmonary Arterial

Background. Pulmonary arterial hypertension (PAH) is a disease or pathophysiological syndrome which has a low survival rate with abnormally elevated pulmonary artery pressure caused by known or unknown reasons. In addition, the pathogenesis of PAH is not fully understood. Therefore, it has become an urgent matter to search for clinical molecular markers of PAH, study the pathogenesis of PAH, and contribute to the development of new science-based PAH diagnosis and targeted treatment methods. Methods. In this study, the Gene Expression Omnibus (GEO) database was used to downloaded a microarray dataset about PAH, and the differentially expressed genes (DEGs) between PAH and normal control were screened out. Moreover, we performed the functional enrichment analyses and protein-protein interaction (PPI) network analyses of the DEGs. In addition, the prediction of miRNA and transcriptional factor (TF) of hub genes and construction miRNA-TF-hub gene network were performed. Besides, the ROC curve was used to evaluate the diagnostic value of hub genes. Finally, the potential drug targets for the 5 identified hub genes were screened out. Results. 69 DEGs were identified between PAH samples and normal samples. GO and KEGG pathway analyses revealed that these DEGs were mostly enriched in the inflammatory response and cytokine-cytokine receptor interaction, respectively. The miRNA-hub genes network was conducted subsequently with 131 miRNAs, 7 TFs, and 5 hub genes (CCL5, CXCL12, VCAM1, CXCR1, and SPP1) which screened out via constructing the PPI network. 17 drugs interacted with 5 hub genes were identified. Conclusions. Through bioinformatic analysis of microarray data sets, 5 hub genes (CCL5, CXCL12, VCAM1, CXCR1, and SPP1) were identified from DEGs between control samples and PAH samples. Studies showed that the five hub genes might play an important role in the development of PAH. These 5 hub genes might be potential biomarkers for diagnosis or targets for the treatment of PAH. In addition, our work also indicated that paying more attention on studies based on these 5 hub genes might help to understand the molecular mechanism of the development of PAH.

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 Identification and Analysis of Key Genes Associated with Ulcerative Colitis by Integrated Bioinformatics Methods

2021 ◽  
Author(s):  
Xingyu Yu ◽  
Jinjie Li ◽  
Hongci Chen ◽  
Xingmeng Chen ◽  
Yu Xiang
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Protein Interaction ◽  
Chemokine Receptor ◽  
Cytokine Receptor ◽  
Receptor Type ◽  
Receptor Interaction ◽  
Potential Candidate ◽  
Hub Genes

Abstract Background: Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa. The exact mechanism of the disease still remains unclear. Here we tried to explore new biomarkers and potential therapeutic targets in UC through adopting integrated bioinformatics tools.Results: By performing DEGs analysis, 59 upregulated and 39 downregulated DEGs were successfully identified from GSE3365, respectively. And they were mainly enriched in the terms of Cytokine-cytokine receptor interaction,Viral protein interaction with cytokine and cytokine receptor,Pantothenate and CoA biosynthesis,IL-17 signaling pathway and Chemokine signaling pathway. Based on the data of protein–protein interaction (PPI), the top 10 hub genes were ranked, including Growth-regulated alpha protein (CXCL1), C-C motif chemokine 2 (CCL2), C-X-C chemokine receptor type 1 (CXCR1), Low affinity immunoglobulin gamma Fc region receptor III-B (FCGR3B), C-X-C chemokine receptor type 2 (CXCR2), Prostaglandin G/H synthase 2 (PTGS2), Triggering receptor expressed on myeloid cells 1 (TREM1), Interleukin-1 receptor type 1 (IL1R1), fMet-Leu-Phe receptor (FPR1), and Band 3 anion transport protein (SLC4A1).What’s more, the results of correlation analysis demonstrated that there was a positive correlation between the 10 hub DEGs.Conclusion: Ten DEGs were identified as potential candidate diagnostic biomarkers for patients with UC in present study. However, further experiments are needed to confirm the functional pathways and hub genes associated with UC.

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