Correction to ‘The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets’

Szklarczyk, Damian; Gable, Annika L.; Nastou, Katerina C.; Lyon, David; Kirsch, Rebecca; Pyysalo, Sampo; Doncheva, Nadezhda T.; Legeay, Marc; Fang, Tao; Bork, Peer; Jensen, Lars Juhl; Mering, Christian von

doi:10.1093/nar/gkab835

Cited by 313 publications

(211 citation statements)

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“…The EMT score in this study was calculated according to our previous study [25]. Protein-protein interaction analysis was performed with STRING [26,27].…”

Section: In-silico Data Analysismentioning

confidence: 99%

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Cox

Sarafraz-Yazdi

et al. 2021

Cancers

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The aim of this study was to assess the effects of pirfenidone (PFD) on promoting epithelial–mesenchymal-transition (EMT) and stemness features in breast carcinoma cells through targeting cancer-associated-fibroblasts (CAFs). Using The Cancer Genome Atlas (TCGA) database, we analyzed the association between stromal index, EMT, and stemness-related genes across 1084 breast cancer patients, identifying positive correlation between YAP1, EMT, and stemness genes in samples with a high-stromal index. We monitored carcinoma cell invasion and spheroid formation co-cultured with CAFs in a 3D microfluidic device, followed by exposing carcinoma cells, spheroids, and CAFs with PFD. We depicted a positive association between the high-stromal index and the expression of EMT and stemness genes. High YAP1 expression in samples correlated with more advanced EMT status and stromal index. Additionally, we found that CAFs promoted spheroid formation and induced the expression of YAP1, VIM, and CD44 in spheroids. Treatment with PFD reduced carcinoma cell migration and decreased the expression of these genes at the protein level. The cytokine profiling showed significant depletion of various EMT- and stemness-regulated cytokines, particularly IL8, CCL17, and TNF-beta. These data highlight the potential application of PFD on inhibiting EMT and stemness in carcinoma cells through the targeting of critical cytokines.

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“…The EMT score in this study was calculated according to our previous study [25]. Protein-protein interaction analysis was performed with STRING [26,27].…”

Section: In-silico Data Analysismentioning

confidence: 99%

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Cox

Sarafraz-Yazdi

et al. 2021

Cancers

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“…An enriched module is based on the PPI network with a cutoff criterion of MCODE score > 4. A connected node indicates that the two proteins that jointly contribute to a specific cellular process are considered functionally associated [42]. The results showed that all the biomarker candidates are organically related.…”

Section: Discussionmentioning

confidence: 96%

Identification and Characterization of mRNA Biomarkers for Sodium Cyanide Exposure

Kim

Jee

Kim

et al. 2021

Toxics

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Biomarkers in exposure assessment are defined as the quantifiable targets that indicate the exposure to hazardous chemicals and their resulting health effect. In this study, we aimed to identify, validate, and characterize the mRNA biomarker that can detect the exposure of sodium cyanide. To identify reliable biomarkers for sodium cyanide exposure, critical criteria were defined for candidate selection: (1) the expression level of mRNA significantly changes in response to sodium thiocyanate treatment in transcriptomics results (fold change > 2.0 or <0.50, adjusted p-value < 0.05); and (2) the mRNA level is significantly modulated by sodium cyanide exposure in both normal human lung cells and rat lung tissue. We identified the following mRNA biomarker candidates: ADCY5, ANGPTL4, CCNG2, CD9, COL1A2, DACT3, GGCX, GRB14, H1F0, HSPA1A, MAF, MAT2A, PPP1R10, and PPP4C. The expression levels of these candidates were commonly downregulated by sodium cyanide exposure both in vitro and in vivo. We functionally characterized the biomarkers and established the impact of sodium cyanide on transcriptomic profiles using in silico approaches. Our results suggest that the biomarkers may contribute to the regulation and degradation of the extracellular matrix, leading to a negative effect on surrounding lung cells.

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“…Topology analysis of networks was carried out according to the values of degree centrality, betweenness centrality, and closeness centrality. The protein-protein interaction data set comes from the stringdb database ( https://cn.string-db.org/ ) (Department of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich) ( 20 ).…”

Section: Methodsmentioning

confidence: 99%

The Potential Bioactive Components of Nine TCM Prescriptions Against COVID-19 in Lung Cancer Were Explored Based on Network Pharmacology and Molecular Docking

Xiao

et al. 2022

Front. Med.

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ObjectiveThe purpose of this study was to screen active components and molecular targets of nine prescriptions recommended by the National Health Commission (NHC) of China by network pharmacology, and to explore the potential mechanism of the core active components against COVID-19 with molecular docking.MethodsDifferentially expressed genes of lung adenocarcinoma (LUAD) screened by edgeR analysis were overlapped with immune-related genes in MMPORT and COVID-19-related genes in GeneCards. The overlapped genes were also COVID-19 immune-related genes in LUAD. TCMSP platform was used to identify active ingredients of the prescription, potential targets were identified by the UniProt database, and the cross genes with COVID-19 immune-related genes in LUAD were used to construct a Chinese Medicine-Logy-immune target network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the target genes of each prescription. Finally, the key active components were selected for molecular docking simulation with ACE2.ResultsWe obtained 15 overlapping immunization target genes from FPQXZ, HSYFZ, HSZFZ, and QFPDT, 16 overlapping immunization target genes from QYLFZ, SDYFZ, SRYFZ, and YDBFZ, and 17 overlapping immunization target genes from QYLXZ. ADRB2, FOS, HMOX1, ICAM1, IL6, JUN, NFKBIA, and STAT1 also had the highest-ranked therapeutic targets for 9 prescriptions, and their expressions were positively correlated with TME-related stromal score, immune score, and ESTIMATE score. Among 9 compounds with the highest frequency of occurrence in the 9 prescriptions, baicalein had the highest ACE2 binding affinity and can be well-combined into the active pocket of ACE2 It is stabilized by forming hydrogen bonds with ASN290 and ILE291 in ACE2 and hydrophobic interaction with PHE438, ILE291, and PRO415.ConclusionThe nine Chinese medicine prescriptions may play an anti-SARS-CoV-2 role via regulating viral transcription and immune function through multi-component, multi-target, and multi-pathway.

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Correction to ‘The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets’

Cited by 313 publications

References 0 publications

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Pirfenidone Reduces Epithelial–Mesenchymal Transition and Spheroid Formation in Breast Carcinoma through Targeting Cancer-Associated Fibroblasts (CAFs)

Identification and Characterization of mRNA Biomarkers for Sodium Cyanide Exposure

The Potential Bioactive Components of Nine TCM Prescriptions Against COVID-19 in Lung Cancer Were Explored Based on Network Pharmacology and Molecular Docking

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