Integrated Analysis of Microbe-Host Interactions in Crohn's Disease Reveals Potential Mechanistic Effects of Microbial Proteins on Host Gene Expression

Abstract Background In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. Methods We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. Results We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. Conclusion The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD.

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Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression

Science Advances ◽

10.1126/sciadv.abe7386 ◽

2021 ◽

Vol 7 (6) ◽

pp. eabe7386 ◽

Cited By ~ 3

Author(s):

Ke Zhang ◽

Lisa Miorin ◽

Tadashi Makio ◽

Ishmael Dehghan ◽

Shengyan Gao ◽

...

Keyword(s):

Gene Expression ◽

Nuclear Export ◽

Messenger Rna ◽

Mrna Export ◽

Host Gene ◽

Nuclear Pore ◽

Host Gene Expression ◽

Host Interactions ◽

Inhibitory Function ◽

Cellular Mrnas

The ongoing unprecedented severe acute respiratory syndrome caused by the SARS-CoV-2 outbreak worldwide has highlighted the need for understanding viral-host interactions involved in mechanisms of virulence. Here, we show that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, which is responsible for nuclear export of cellular mRNAs. Nsp1 prevents proper binding of NXF1 to mRNA export adaptors and NXF1 docking at the nuclear pore complex. As a result, a significant number of cellular mRNAs are retained in the nucleus during infection. Increased levels of NXF1 rescues the Nsp1-mediated mRNA export block and inhibits SARS-CoV-2 infection. Thus, antagonizing the Nsp1 inhibitory function on mRNA export may represent a strategy to restoring proper antiviral host gene expression in infected cells.

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Identification of key genes and pathways associated with Crohn’s disease by bioinformatics analysis

10.1101/543835 ◽

2019 ◽

Author(s):

Zheng Wang ◽

Jie Zhu ◽

Lixian Ma

Keyword(s):

Gene Expression ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Signaling Pathways ◽

Bioinformatics Analysis ◽

Integrated Analysis ◽

Functional Modules ◽

Disease Pathogenesis ◽

Black Module ◽

Key Genes

AbstractCrohn’s disease is a type of inflammatory bowel disease posing a significant threat to human health all over the world. Genome-wide gene expression profiles of mucosal colonic biopsies have provided some insight into the molecular mechanisms of Crohn’s disease. However, the exact pathogenesis is unclear. This study aimed to identify key genes and significant signaling pathways associated with Crohn’s disease by bioinformatics analysis. To identify key genes, an integrated analysis of gene expression signature was conducted using a robust rank aggregation approach. A total of 179 Crohn’s disease patients and 94 healthy controls from nine public microarray datasets were included. MMP1 and CLDN8 were two key genes screened from the differentially expressed genes. Connectivity Map predicted several small molecules as possible adjuvant drugs to treat CD. Besides, we used weighted gene co-expression network analysis to explore the co-expression modules associated with Crohn’s disease pathogenesis. Seven main functional modules were identified, of which black module showed the highest correlation with Crohn’s disease. The genes in black module mainly enriched in Interferon Signaling and defense response to virus. Blue module was another important module and enriched in several signaling pathways, including extracellular matrix organization, inflammatory response and blood vessel development. There were also several other meaningful functional modules which enriched in many biological processes. The present study identified a number of key genes and pathways correlated with Crohn’s disease and potential drugs to combat it, which might offer insights into Crohn’s disease pathogenesis and provide a clue to potential treatments.

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