Human HtrA, an Evolutionarily Conserved Serine Protease Identified as a Differentially Expressed Gene Product in Osteoarthritic Cartilage

Background: Psoriasis is a chronic immune mediated skin disorder with global prevalence of 0.2- 11.4%. Despite rare mortality, the severity of the disease could be understood by the accompanying comorbidities, that has even led to psychological problems among several patients. The cause and the disease mechanism still remain elusive. Objective: To identify potential therapeutic targets and affecting pathways for better insight of the disease pathogenesis. Method: The gene expression profile GSE13355 and GSE14905 were retrieved from NCBI, Gene Expression Omnibus database. The GEO profiles were integrated and the DEGs of lesional and non-lesional psoriasis skin were identified using the affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes pathways of the DEGs were analyzed using clusterProfiler. Cytoscape, V3.7.1 was utilized to construct protein interaction network and analyze the interactome map of candidate proteins encoded in DEGs. Functionally relevant clusters were detected through Cytohubba and MCODE. Results: A total of 1013 genes were differentially expressed in lesional skin of which 557 were upregulated and 456 were downregulated. Seven dysregulated genes were extracted in non-lesional skin. The disease gene network of these DEGs revealed 75 newly identified differentially expressed gene that might have a role in development and progression of the disease. GO analysis revealed keratinocyte differentiation and positive regulation of cytokine production to be the most enriched biological process and molecular function. Cytokines -cytokine receptor was the most enriched pathways. Among 1013 identified DEGs in lesional group, 36 DEGs were found to have altered genetic signature including IL1B and STAT3 which are also reported as hub genes. CCNB1, CCNA2, CDK1, IL1B, CXCL8, MKI 67, ESR1, UBE2C, STAT1 and STAT3 were top 10 hub gene. Conclusion: The hub genes, genomic altered DEGs and other newly identified differentially dysregulated genes would improve our understanding of psoriasis pathogenesis, moreover, the hub genes could be explored as potential therapeutic targets for psoriasis.

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Identification of the Differentially Expressed Genes Involved in the Synergistic Neurotoxicity of an HIV Protease Inhibitor and Methamphetamine

Current HIV Research ◽

10.2174/1570162x17666190924200354 ◽

2019 ◽

Vol 17 (4) ◽

pp. 290-303

Author(s):

Sangsang Li ◽

Yanfei Li ◽

Bingpeng Deng ◽

Jie Yan ◽

Yong Wang

Keyword(s):

Protease Inhibitor ◽

Growth Inhibition ◽

Quantitative Polymerase Chain Reaction ◽

Differentially Expressed Gene ◽

Antiretroviral Drugs ◽

Differentially Expressed ◽

Hiv Protease ◽

Hiv Protease Inhibitor ◽

Dopaminergic Cells ◽

Immunodeficiency Syndrome

Background: The abuse of psychostimulants such as methamphetamine (METH) is common in human immunodeficiency virus (HIV)-infected individuals. Acquired immunodeficiency syndrome (AIDS) patients taking METH and antiretroviral drugs could suffer severe neurologic damage and cognitive impairment. Objective: To reveal the underlying neuropathologic mechanisms of an HIV protease inhibitor (PI) combined with METH, growth-inhibition tests of dopaminergic cells and RNA sequencing were performed. Methods: A combination of METH and PI caused more growth inhibition of dopaminergic cells than METH alone or a PI alone. Furthermore, we identified differentially expressed gene (DEG) patterns in the METH vs. untreated cells (1161 genes), PI vs. untreated cells (16 genes), METH-PI vs. PI (3959 genes), and METH-PI vs. METH groups (14 genes). Results: The DEGs in the METH-PI co-treatment group were verified in the brains of a mouse model using quantitative polymerase chain reaction and were involved mostly in the regulatory functions of cell proliferation and inflammation. Conclusion: Such identification of key regulatory genes could facilitate the study of their neuroprotective potential in the users of METH and PIs.

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Gene Set Correlation Analysis and Visualization Using Gene Expression Data

Current Bioinformatics ◽

10.2174/1574893615999200629124444 ◽

2020 ◽

Vol 15 ◽

Author(s):

Chen-An Tsai ◽

James J. Chen

Keyword(s):

Gene Expression ◽

Correlation Analysis ◽

Gene Expression Data ◽

Differentially Expressed Gene ◽

Differentially Expressed ◽

Superior Performance ◽

Expression Data ◽

Gene Set ◽

Gene Sets ◽

Set Correlation

Background: Gene set enrichment analyses (GSEA) provide a useful and powerful approach to identify differentially expressed gene sets with prior biological knowledge. Several GSEA algorithms have been proposed to perform enrichment analyses on groups of genes. However, many of these algorithms have focused on identification of differentially expressed gene sets in a given phenotype. Objective: In this paper, we propose a gene set analytic framework, Gene Set Correlation Analysis (GSCoA), that simultaneously measures within and between gene sets variation to identify sets of genes enriched for differential expression and highly co-related pathways. Methods: We apply co-inertia analysis to the comparisons of cross-gene sets in gene expression data to measure the costructure of expression profiles in pairs of gene sets. Co-inertia analysis (CIA) is one multivariate method to identify trends or co-relationships in multiple datasets, which contain the same samples. The objective of CIA is to seek ordinations (dimension reduction diagrams) of two gene sets such that the square covariance between the projections of the gene sets on successive axes is maximized. Simulation studies illustrate that CIA offers superior performance in identifying corelationships between gene sets in all simulation settings when compared to correlation-based gene set methods. Result and Conclusion: We also combine between-gene set CIA and GSEA to discover the relationships between gene sets significantly associated with phenotypes. In addition, we provide a graphical technique for visualizing and simultaneously exploring the associations of between and within gene sets and their interaction and network. We then demonstrate integration of within and between gene sets variation using CIA and GSEA, applied to the p53 gene expression data using the c2 curated gene sets. Ultimately, the GSCoA approach provides an attractive tool for identification and visualization of novel associations between pairs of gene sets by integrating co-relationships between gene sets into gene set analysis.

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Identification of differentially expressed gene sequences along granulocytic differentiation of promyelocytic HL60 cells

Biochemical Society Transactions ◽

10.1042/bst028a174 ◽

2000 ◽

Vol 28 (5) ◽

pp. A174-A174

Author(s):

A. Kulyté ◽

S. Zuklys ◽

A. Gineitis ◽

G. A. Hollander ◽

K.-E. Magnusson

Keyword(s):

Differentially Expressed Gene ◽

Differentially Expressed ◽

Gene Sequences ◽

Granulocytic Differentiation ◽

Hl60 Cells

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Characterization of FOXF1 as a novel regulator of nodal metastasis in bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.480 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 480-480

Author(s):

Anirban P Mitra ◽

Andrea Kokorovic ◽

Tanner Miest ◽

Vikram M Narayan ◽

Debasish Sundi ◽

...

Keyword(s):

Bladder Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Differentially Expressed Gene ◽

Cancer Cell Lines ◽

Differentially Expressed ◽

Bladder Cancer Cell ◽

Primary Tumors ◽

Orthotopic Xenografts

480 Background: Members of the forkhead transcription factor (FOX) family are important mediators of embryonic development and are known to be altered in a variety of cancers. The functional role of FOXF1 in bladder tumorigenesis and progression has not been clearly characterized thus far. This study investigated the clinical implications of differential FOXF1 expression in bladder cancer, and potential mechanisms by which its alteration can lead to tumor metastasis. Methods: Whole genome expression profiling was performed on paired primary tumors and nodal metastases from a radical cystectomy discovery cohort using Illumina HT12 v3-4 BeadChip arrays to identify FOXF1 as a top differentially expressed gene. Prognostic role of differential FOXF1 expression was validated on two independent cystectomy cohorts. Differential FOXF1 expression was also evaluated in murine orthotopic xenografts. Small interfering RNA was used to knock down FOXF1 in RT112 and UC6 bladder cancer cell lines to develop an in vitro model for assessment of metastatic potential. Next-generation sequencing and hierarchical clustering analysis were used to identify differentially altered genes secondary to FOXF1 knockdown. 186 biologically curated pathways were interrogated with internal validation to elucidate the downstream biologic mechanisms of metastasis. Results: In the discovery cohort, FOXF1 was a top differentially expressed gene with 3.6-fold lower expression in nodal metastases than paired primary tumors (n = 33, p < 0.001). Multivariable analyses in two validation cohorts (total n = 128) indicated that FOXF1 underexpression was associated with worse cancer-specific (p = 0.046) and overall survival (p = 0.006). Murine orthotopic xenografts (n = 13) established from human bladder cancer cell lines (UC3, UC6, UC14) showed FOXF1 underexpression in metastatic deposits compared with primary tumors (p = 0.004). Hierarchical clustering identified 40 differentially expressed genes between FOXF1-knockdown bladder cancer cell lines and their corresponding controls. Biological pathway interrogation showed differential enrichment for genes associated with mitogen-activated protein kinase signaling, focal adhesion and other carcinogenic pathways in FOXF1-knockdown cells compared with controls (normalized enrichment score ≥ 1.3). Conclusions: We identify and characterize FOXF1 as a novel regulatory molecule that potentially drives bladder cancer metastasis. This may be modulated through alterations in intracellular signaling and cellular adhesion. FOXF1 may serve as a prognostic biomarker that can identify patients at impending risk for metastasis who may benefit from more aggressive management.

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