scholarly journals Identification of the Potential Biomarkers Involved in the Human Oral Mucosal Wound Healing: A Bioinformatic Study

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Wanchen Ning ◽  
Xiao Jiang ◽  
Zhengyang Sun ◽  
Anthony Chukwunonso Ogbuehi ◽  
Wenli Gu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Oral Mucosa ◽  
Mirna Target ◽  
Interaction Network ◽  
Epigenetic Mechanisms ◽  
Ppi Network ◽  
Mucosal Wound

Objective. To identify the key genetic and epigenetic mechanisms involved in the wound healing process after injury of the oral mucosa. Materials and Methods. Gene expression profiling datasets pertaining to rapid wound healing of oral mucosa were identified using the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed to identify differentially expressed genes (DEGs) during oral mucosal wound healing. Next, functional enrichment analysis was performed to identify the biological processes (BPs) and signaling pathways relevant to these DEGs. A protein-protein interaction (PPI) network was constructed to identify hub DEGs. Interaction networks were constructed for both miRNA-target DEGs and DEGs-transcription factors. A DEGs-chemical compound interaction network and a miRNA-small molecular interaction network were also constructed. Results. DEGs were found significantly enriched in several signaling pathways including arachidonic acid metabolism, cell cycle, p53, and ECM-receptor interaction. Hub genes, GABARAPL1, GABARAPL2, HDAC5, MAP1LC3A, AURKA, and PLK1, were identified via PPI network analysis. Two miRNAs, miR-34a-5p and miR-335-5p, were identified as pivotal players in the miRNA-target DEGs network. Four transcription factors FOS, PLAU, BCL6, and RORA were found to play key roles in the TFs-DEGs interaction network. Several chemical compounds including Valproic acid, Doxorubicin, Nickel, and tretinoin and small molecular drugs including atorvastatin, 17β-estradiol, curcumin, and vitamin D3 were noted to influence oral mucosa regeneration by regulating the expression of healing-associated DEGs/miRNAs. Conclusion. Genetic and epigenetic mechanisms and specific drugs were identified as significant molecular mechanisms and entities relevant to oral mucosal healing. These may be valuable potential targets for experimental research.

scholarly journals Transcriptome Analysis of Hypertrophic Heart Tissues from Murine Transverse Aortic Constriction and Human Aortic Stenosis Reveals Key Genes and Transcription Factors Involved in Cardiac Remodeling Induced by Mechanical Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Peng Yu ◽  
Baoli Zhang ◽  
Ming Liu ◽  
Ying Yu ◽  
Ji Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Aortic Stenosis ◽  
Mechanical Stress ◽  
Cardiac Remodeling ◽  
Interaction Network ◽  
Cytokine Signaling ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Genomic Changes

Background. Mechanical stress-induced cardiac remodeling that results in heart failure is characterized by transcriptional reprogramming of gene expression. However, a systematic study of genomic changes involved in this process has not been performed to date. To investigate the genomic changes and underlying mechanism of cardiac remodeling, we collected and analyzed DNA microarray data for murine transverse aortic constriction (TAC) and human aortic stenosis (AS) from the Gene Expression Omnibus database and the European Bioinformatics Institute. Methods and Results. The differential expression genes (DEGs) across the datasets were merged. The Venn diagrams showed that the number of intersections for early and late cardiac remodeling was 74 and 16, respectively. Gene ontology and protein–protein interaction network analysis showed that metabolic changes, cell differentiation and growth, cell cycling, and collagen fibril organization accounted for a great portion of the DEGs in the TAC model, while in AS patients’ immune system signaling and cytokine signaling displayed the most significant changes. The intersections between the TAC model and AS patients were few. Nevertheless, the DEGs of the two species shared some common regulatory transcription factors (TFs), including SP1, CEBPB, PPARG, and NFKB1, when the heart was challenged by applied mechanical stress. Conclusions. This study unravels the complex transcriptome profiles of the heart tissues and highlighting the candidate genes involved in cardiac remodeling induced by mechanical stress may usher in a new era of precision diagnostics and treatment in patients with cardiac remodeling.

scholarly journals Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells

2007 ◽  
Vol 293 (2) ◽  
pp. L480-L490 ◽  
Author(s):  
Jinming Zhao ◽  
Richart Harper ◽  
Aaron Barchowsky ◽  
Y. P. Peter Di
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Dna Binding ◽  
Signaling Pathways ◽  
Tobacco Smoke ◽  
Mapk Signaling ◽  
Regulation Of Transcription ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Mapk Signaling Pathways

Activation and regulation of transcription factors (TFs) are the major mechanisms regulating changes in gene expression upon environmental exposure. Tobacco smoke (TS) is a complex mixture of chemicals, each of which could act through different signal cascades, leading to the regulation of distinct TFs and alterations in subsequent gene expression. We proposed that TS exposure affects inflammatory gene expression at the transcriptional level by modulating the DNA binding activities of TFs. To investigate transcriptional regulation upon TS exposure, a protein/DNA array was applied to screen TFs that are affected by TS exposure. This array-based screening allowed us to simultaneously detect 244 different TFs. Our results indicated that multiple TFs were rapidly activated upon TS exposure. DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our results showed that at least 20 TFs displayed more than twofold expressional changes after smoke treatment. Ten smoke-induced TFs, including NF-κB, VDR, ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-κB family, which is involved in inflammation-induced gene activation, was selected for further study to characterize TS exposure-induced transcriptional activation. Western blot analysis and immunofluorescence microscopy indicated that TS exposure induced phosphorylation of IκB and translocation of NF-κB p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK signaling pathways by TS exposure increased transcriptional activity of NF-κB. These data provide a potential mechanism for TS-induced inflammatory gene expression.

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 Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Christopher S. Anderson ◽  
Marta L. DeDiego ◽  
David J. Topham ◽  
Juilee Thakar
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Influenza A ◽  
New Caledonia ◽  
Expression Profiles ◽  
Influenza Infection ◽  
Interaction Network ◽  
H1n1 Influenza ◽  
Boolean Model ◽  
Boolean Logic

Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets) have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV) infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC) infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection.

scholarly journals Investigation of Aberrantly Methylated Differentially Expressed Genes in Pancreatic Cancer by Integrated Bioinformatics Analysis

2021 ◽  
Author(s):  
Cailin xue ◽  
Peng gao ◽  
Xudong zhang ◽  
Xiaohan cui ◽  
Lei jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Dna Sequences ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Biological Processes ◽  
Ppi Network ◽  
Hub Genes

Abstract Background: Abnormal methylation of DNA sequences plays an important role in the development and progression of pancreatic cancer (PC). The purpose of this study was to identify abnormal methylation genes and related signaling pathways in PC by comprehensive bioinformatic analysis of three datasets in the Gene Expression Omnibus (GEO). Methods: Datasets of gene expression microarrays (GSE91035, GSE15471) and gene methylation microarrays (GSE37480) were downloaded from the GEO database. Aberrantly methylated-differentially expressed genes (DEGs) were analysis by GEO2R software. GO and KEGG enrichment analyses of selected genes were performed using DAVID database. A protein–protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. Core module analysis was performed by Mcode in Cytoscape. Hub genes were obtained by CytoHubba app. in Cytoscape software. Results: A total of 267 hypomethylation-high expression genes, which were enriched in biological processes of cell adhesion, biological adhesion and regulation of signaling were obtained. KEGG pathway enrichment showed ECM-receptor interaction, Focal adhesion and PI3K-Akt signaling pathway. The top 5 hub genes of PPI network were EZH2, CCNA2, CDC20, KIF11, UBE2C. As for hypermethylation-low expression genes, 202 genes were identified, which were enriched in biological processes of cellular amino acid biosynthesis process and positive regulation of PI3K activity, etc. The pathways enriched were the pancreatic secretion and biosynthesis of amino acids pathways, etc. The five significant hub genes were DLG3, GPT2, PLCB1, CXCL12 and GNG7. In addition, five genes, including CCNA2, KIF11, UBE2C, PLCB1 and GNG7, significantly associated with patient's prognosis were also identified. Conclusion: Novel genes with abnormal expression were identified, which will help us further understand the molecular mechanism and related signaling pathways of PC, and these aberrant genes could possibly serve as biomarkers for precise diagnosis and treatment of PC.

scholarly journals Site-Specific Expression Pattern of PIWI-Interacting RNA in Skin and Oral Mucosal Wound Healing

2020 ◽  
Vol 21 (2) ◽  
pp. 521
Author(s):  
Chen ◽  
Chen ◽  
Simões ◽  
Wu ◽  
Dai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Repair ◽  
Healing Process ◽  
Wound Healing Process ◽  
Site Specific ◽  
Mucosal Epithelium ◽  
Tissue Specific ◽  
Mucosal Wound

The oral mucosa exhibits exceptional healing capability when compared to skin. Recent studies suggest that intrinsic differences in coding genes and regulatory small non-coding RNA (sncRNA) genes (e.g., microRNAs) may underlie the exceptional healing that occurs in the oral mucosa. Here, we investigate the role of a novel class of sncRNA—Piwi-interacting RNA (piRNA)—in the tissue-specific differential response to injury. An abundance of piRNAs was detected in both skin and oral mucosal epithelium during wound healing. The expression of PIWI genes (the obligate binding partners of piRNAs) was also detected in skin and oral wound healing. This data suggested that PIWI-piRNA machinery may serve an unknown function in the highly orchestrated wound healing process. Furthermore, unique tissue-specific piRNA profiles were obtained in the skin and oral mucosal epithelium, and substantially more changes in piRNA expression were observed during skin wound healing than oral mucosal wound healing. Thus, we present the first clue suggesting a role of piRNA in wound healing, and provide the first site-specific piRNA profile of skin and oral mucosal wound healing. These results serve as a foundation for the future investigation of the functional contribution(s) of piRNA in wound repair and tissue regeneration.

scholarly journals Migration and Adhesion of B-Lymphocytes to Specific Microenvironments in Mantle Cell Lymphoma: Interplay between Signaling Pathways and the Epigenetic Landscape

2021 ◽  
Vol 22 (12) ◽  
pp. 6247
Author(s):  
Laia Sadeghi ◽  
Anthony P. Wright
Keyword(s):  
Gene Expression ◽  
Mantle Cell Lymphoma ◽  
Signaling Pathways ◽  
Chemokine Receptors ◽  
Cell Lymphoma ◽  
Gene Expression Pattern ◽  
Epigenetic Mechanisms ◽  
Epigenetic Landscape ◽  
Lymphocyte Migration ◽  
Mantle Cell

Lymphocyte migration to and sequestration in specific microenvironments plays a crucial role in their differentiation and survival. Lymphocyte trafficking and homing are tightly regulated by signaling pathways and is mediated by cytokines, chemokines, cytokine/chemokine receptors and adhesion molecules. The production of cytokines and chemokines is largely controlled by transcription factors in the context of a specific epigenetic landscape. These regulatory factors are strongly interconnected, and they influence the gene expression pattern in lymphocytes, promoting processes such as cell survival. The epigenetic status of the genome plays a key role in regulating gene expression during many key biological processes, and it is becoming more evident that dysregulation of epigenetic mechanisms contributes to cancer initiation, progression and drug resistance. Here, we review the signaling pathways that regulate lymphoma cell migration and adhesion with a focus on Mantle cell lymphoma and highlight the fundamental role of epigenetic mechanisms in integrating signals at the level of gene expression throughout the genome.

scholarly journals The PathLinker app: Connect the dots in protein interaction networks

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 58 ◽  
Author(s):  
Daniel P. Gil ◽  
Jeffrey N. Law ◽  
T. M. Murali
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Graph Theoretic ◽  
Manual Curation

PathLinker is a graph-theoretic algorithm for reconstructing the interactions in a signaling pathway of interest. It efficiently computes multiple short paths within a background protein interaction network from the receptors to transcription factors (TFs) in a pathway. We originally developed PathLinker to complement manual curation of signaling pathways, which is slow and painstaking. The method can be used in general to connect any set of sources to any set of targets in an interaction network. The app presented here makes the PathLinker functionality available to Cytoscape users. We present an example where we used PathLinker to compute and analyze the network of interactions connecting proteins that are perturbed by the drug lovastatin.

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