Network based analyses of gene expression profile of LCN2 overexpression in esophageal squamous cell carcinoma

Wu, Bing‐Li; Li, Chunquan; Du, Zhifeng; Yao, Qianlan; Wu, Jian‐Yi; Li, Feng; Zhang, Pi‐Xian; Li, Shang; Xu, Li‐Yan; Li, En‐Min

doi:10.1038/srep05403

Cited by 30 publications

(25 citation statements)

References 45 publications

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“…Topological parameters were analyzed by NetworkAnalyzer, which would provide insight into the organization and structure of the complex network [12]. The power law of distribution of node degrees, one of most important network topological characteristics, was analyzed as we described previously [13].…”

Section: Analyses Of the Ppin Topological Parametersmentioning

confidence: 99%

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

Xia¹,

Chen²,

Zhou³

et al. 2020

Preprint

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Background The novel coronavirus SARS-CoV-2 pandemic has infected more than 10 million people, killed over 500,000 so far. Currently, no effective drugs are available to treat this infectious disease, due to limited knowledge of the molecular mechanisms of SARS-CoV-2 infection. ACE2 (angiotensin I converting enzyme 2) has long been identified as the major receptor for coronavirus entry the host cells. Methods In this study, we constructed the protein-protein interaction networks (PPIN) based on ACE2 and its interacting proteins, combined with the expression change and co-expression relationship. The potential drugs targeting the proteins in the PPIN were explored.Results ACE2 and its interacting proteins AAMP and HRAS are obviously increased, and their PPIN show distinguishing expression patterns during the COVID-19 progression. At least six pathways are activated for the host cell in the response to the virus. Moreover, drug-target networks were built to provide important clues to block ACE2 and its interacting proteins. Except the reported four drugs for ACE2, its interacting protein CALM1 and HRAS are great potentially druggable. We also considered the path initiated from ACE2 to nucleus by cascades of interaction, especially for the transcription factors in the PPIN which are also druggable. Conclusion In summary, this study provides new insight into the disruption of the biological response to virus mediated by ACE2, but also its cascade interacting proteins when considering of PPIN.

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Section: Analyses Of the Ppin Topological Parametersmentioning

confidence: 99%

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

Xia¹,

Chen²,

Zhou³

et al. 2020

Preprint

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“…NGAL has been shown to be an important mediator of invasion and metastasis in ESCC (5,6,10). However, for a improved understanding of the role of NGAL in ESCC, a comprehensive analysis of the mRNA profile of NGAL overexpression ESCC cells was conducted in the present study, using multiple bioinformatic analyses.…”

Section: Discussionmentioning

confidence: 99%

Functional analysis of the mRNA profile of neutrophil gelatinase-associated lipocalin overexpression in esophageal squamous cell carcinoma using multiple bioinformatic tools

et al. 2014

Molecular Medicine Reports

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Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin superfamily; dysregulated expression of NGAL has been observed in several benign and malignant diseases. In the present study, differentially expressed genes, in comparison with those of control cells, in the mRNA expression profile of EC109 esophageal squamous cell carcinoma (ESCC) cells following NGAL overexpression were analyzed by multiple bioinformatic tools for a comprehensive understanding. A total of 29 gene ontology (GO) terms associated with immune function, chromatin structure and gene transcription were identified among the differentially expressed genes (DEGs) in NGAL overexpressing cells. In addition to the detected GO categories, the results from the functional annotation chart revealed that the differentially expressed genes were also associated with 101 functional annotation category terms. A total of 59 subpathways associated locally with the differentially expressed genes were identified by subpathway analysis, a markedly greater total that detected by traditional pathway enrichment analysis only. Promoter analysis indicated that the potential transcription factors Snail, deltaEF1, Mycn, Arnt, MNB1A, PBF, E74A, Ubx, SPI1 and GATA2 were unique to the downregulated DEG promoters, while bZIP910, ZNF42 and SOX9 were unique for the upregulated DEG promoters. In conclusion, the understanding of the role of NGAL overexpression in ESCC has been improved through the present bioinformatic analysis.

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“…It is noteworthy that among the known protein families in the 2009 Pfam database only 1.4% are considered allergens . In the case of respiratory mammalian allergens a few protein families are absolutely dominant: lipocalins, secretoglobins and kallikreins , and IgE levels against them correlate with the severity of asthma .…”

Section: The Current View On Immune Tolerance Vs Th2 Skewing Of Allermentioning

confidence: 99%

“…Major sources of (at least the human) LCN2 are the liver and macrophages , with sphingosin‐1‐phosphate inducing its production. Lipocalins are elevated and released during inflammation , infections and sepsis , especially when the urinary tract is affected in humans and dogs ; in cardiovascular inflammation they get overexpressed in the brain and linked with depression ; in cancer LCN2 is overexpressed prompting interaction with metalloproteinase‐9 (MMP‐9) , but only LCN2 is prognostic . In the immunosuppressive environment of the tumor stroma LCN2 cooperates with CCL2 to induce immunoregulatory DCs and subsequently CD4(+)FoxP3(+) Treg cells and supports metastasis .…”

Section: Comparing Structural Features Of Lipocalinsmentioning

confidence: 99%

Structural similarities of human and mammalian lipocalins, and their function in innate immunity and allergy

Jensen‐Jarolim

Pacios

Bianchini

et al. 2015

Allergy

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Owners and their domestic animals via skin shedding and secretions, mutually exchange microbiomes, potential pathogens and innate immune molecules. Among the latter especially lipocalins are multifaceted: they may have an immunomodulatory function and, furthermore, they represent one of the most important animal allergen families. The amino acid identities, as well as their structures by superposition modeling were compared among human lipocalins, hLCN1 and hLCN2, and most important animal lipocalin allergens, such as Can f 1, Can f 2 and Can f 4 from dog, Fel d 4 from cats, Bos d 5 from cow's milk, Equ c 1 from horses, and Mus m 1 from mice, all of them representing major allergens. The β‐barrel fold with a central molecular pocket is similar among human and animal lipocalins. Thereby, lipocalins are able to transport a variety of biological ligands in their highly conserved calyx‐like cavity, among them siderophores with the strongest known capability to complex iron (Fe3+). Levels of human lipocalins are elevated in nonallergic inflammation and cancer, associated with innate immunoregulatory functions that critically depend on ligand load. Accordingly, deficient loading of lipocalin allergens establishes their capacity to induce Th2 hypersensitivity. Our similarity analysis of human and mammalian lipocalins highlights their function in innate immunity and allergy.

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Network based analyses of gene expression profile of LCN2 overexpression in esophageal squamous cell carcinoma

Cited by 30 publications

References 45 publications

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

ACE2 Protein-protein Interaction Networks Reveal Potential Druggable Targets for SARS-CoV-2

Functional analysis of the mRNA profile of neutrophil gelatinase-associated lipocalin overexpression in esophageal squamous cell carcinoma using multiple bioinformatic tools

Structural similarities of human and mammalian lipocalins, and their function in innate immunity and allergy

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