scholarly journals A Comprehensive Network Pharmacology-Based Strategy to Investigate Multiple Mechanisms of HeChan Tablet on Lung Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Zhenjie Zhuang ◽  
Qianying Chen ◽  
Cihui Huang ◽  
Junmao Wen ◽  
Haifu Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Network Pharmacology ◽  
Hub Genes ◽  
Lung Cancer Patients ◽  
Ppi Networks

Background. HeChan tablet (HCT) is a traditional Chinese medicine preparation extensively prescribed to treat lung cancer in China. However, the pharmacological mechanisms of HCT on lung cancer remain to be elucidated. Methods. A comprehensive network pharmacology-based strategy was conducted to explore underlying mechanisms of HCT on lung cancer. Putative targets and compounds of HCT were retrieved from TCMSP and BATMAN-TCM databases; related genes of lung cancer were retrieved from OMIM and DisGeNET databases; known therapeutic target genes of lung cancer were retrieved from TTD and DrugBank databases; PPI networks among target genes were constructed to filter hub genes by STRING. Furthermore, the pathway and GO enrichment analysis of hub genes was performed by clusterProfiler, and the clinical significance of hub genes was identified by The Cancer Genome Atlas. Result. A total of 206 compounds and 2,433 target genes of HCT were obtained. 5,317 related genes of lung cancer and 77 known therapeutic target genes of lung cancer were identified. 507 unique target genes were identified among HCT-related genes of lung cancer and 34 unique target genes were identified among HCT-known therapeutic target genes of lung cancer. By PPI networks, 11 target genes AKT1, TP53, MAPK8, JUN, EGFR, TNF, INS, IL-6, MYC, VEGFA, and MAPK1 were identified as major hub genes. IL-6, JUN, EGFR, and MYC were shown to associate with the survival of lung cancer patients. Five compounds of HCT， quercetin, luteolin, kaempferol, beta-sitosterol, and baicalein were recognized as key compounds of HCT on lung cancer. The gene enrichment analysis implied that HCT probably benefitted patients with lung cancer by modulating the MAPK and PI3K-Akt pathways. Conclusion. This study predicted pharmacological and molecular mechanisms of HCT against lung cancer and could pave the way for further experimental research and clinical application of HCT.

scholarly journals A Network Pharmacology-Based Study on the Anti-Lung Cancer Effect of Dipsaci Radix

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jiayan Wu ◽  
Shengkun Hong ◽  
Xiankuan Xie ◽  
Wangmi Liu
Keyword(s):  
Lung Cancer ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Active Compounds

Objective. Dipsaci Radix (DR) has been used to treat fracture and osteoporosis. Recent reports have shown that myeloid cells from bone marrow can promote the proliferation of lung cancer. However, the action and mechanism of DR has not been well defined in lung cancer. The aim of the present study was to define molecular mechanisms of DR as a potential therapeutic approach to treat lung cancer. Methods. Active compounds of DR with oral bioavailability ≥30% and drug-likeness index ≥0.18 were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform. The potential target genes of the active compounds and bone were identified by PharmMapper and GeneCards, respectively. The compound-target network and protein-protein interaction network were built by Cytoscape software and Search Tool for the Retrieval of Interacting Genes webserver, respectively. GO analysis and pathway enrichment analysis were performed using R software. Results. Our study demonstrated that DR had 6 active compounds, including gentisin, sitosterol, Sylvestroside III, 3,5-Di-O-caffeoylquinic acid, cauloside A, and japonine. There were 254 target genes related to these active compounds as well as to bone. SRC, AKT1, and GRB2 were the top 3 hub genes. Metabolisms and signaling pathways associated with these hub genes were significantly enriched. Conclusions. This study indicated that DR could exhibit the anti-lung cancer effect by affecting multiple targets and multiple pathways. It reflects the traditional Chinese medicine characterized by multicomponents and multitargets. DR could be considered as a candidate for clinical anticancer therapy by regulating bone physiological functions.

scholarly journals Circulating or tissue microRNAs and extracellular vesicles as potential lung cancer biomarkers: a systematic review

2017 ◽  
Vol 33 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Yan Song ◽  
Xiuli Yu ◽  
Zongmei Zang ◽  
Guijuan Zhao
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Extracellular Vesicles ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Cancer Biomarkers ◽  
Biological Processes ◽  
Lung Cancer Patients ◽  
Prediction Of Prognosis

For both lung cancer patients and clinical physicians, tumor biomarkers for more efficient early diagnosis and prediction of prognosis are always wanted. Biomarkers in circulating serum, including microRNAs (miRNAs) and extracellular vesicles, hold the greatest possibilities to partially substitute for tissue biopsy. In this systematic review, studies on circulating or tissue miRNAs and extracellular vesicles as potential biomarkers for lung cancer patients were reviewed and are discussed. Furthermore, the target genes of the miRNAs indicated were identified through the miRTarBase, while the relevant biological processes and pathways of miRNAs in lung cancer were analyzed through MiRNA Enrichment Analysis and Annotation (MiEAA). In conclusion, circulating or tissue miRNAs and extracellular vesicles provide us with a window to explore strategies for diagnosing and assessing prognosis and treatment in lung cancer patients.

A Comprehensive Data Analysis of Differentially Regulated Genes in Melanoma

2020 ◽  
Author(s):  
Yanjie Han ◽  
Xinxin Li ◽  
Jiliang Yan ◽  
Chunyan Ma ◽  
Xin Wang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Growth Factor Receptor ◽  
Principal Component ◽  
Distant Metastases ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Ppi Networks

Abstract Background: Melanoma is the most deadly tumor in skin tumors and is prone to distant metastases. The incidence of melanoma has increased rapidly in the past few decades, and current trends indicate that this growth is continuing. This study was aimed to explore the molecular mechanisms of melanoma pathogenesis and discover underlying pathways and genes associated with melanoma.Methods: We used high-throughput expression data to study differential expression profiles of related genes in melanoma. The differentially expressed genes (DEGs) of melanoma in GSE15605, GSE46517, GSE7553 and the Cancer Genome Atlas (TCGA) datasets were analyzed. Differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses and protein–protein interaction (PPI) network construction. After that, we analyzed the differential genes through bioinformatics and got hub genes. Finally, the expression of hub genes was confirmed in the TCGA databases and collected patient tissue samples.Results: Total 144 up-regulated DEGs and 16 down-regulated DEGs were identified. A total of 17 gene ontology analysis (GO) terms and 11 pathways were closely related to melanoma. Pathway of pathways in cancer was enriched in 8 DEGs, such as junction plakoglobin (JUP) and epidermal growth factor receptor (EGFR). In the PPI networks, 9 hub genes were obtained, such as loricrin (LOR), filaggrin (FLG), keratin 5 (KRT5), corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoglein 3 (DSG3), keratin 1 (KRT1), involucrin (IVL) and EGFR. The pathway of pathways in cancer and its enriched DEGs may play important roles in the process of melanoma. The hub genes of DEGs may become promising melanoma candidate genes. Five key genes FLG, DSG1, DSG3, IVL and EGFR were identified in the TCGA database and melanoma tissues.Conclusions: The results suggested that FLG, DSG1, DSG3, IVL and EGFR might play important roles and potentially be valuable in the prognosis and treatment of melanoma.

scholarly journals Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses

2020 ◽  
Author(s):  
Basavaraj Vastrad ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti
Keyword(s):  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Bioinformatics Analyses ◽  
Go Enrichment ◽  
Jakob Disease

AbstractSporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. Pathway and GO enrichment analyses of DEGs were performed. Furthermore, the protein-protein interaction (PPI) network was predicted using the IntAct Molecular Interaction Database and visualized with Cytoscape software. In addition, hub genes and important modules were selected based on the network. Finally, we constructed target genes - miRNA regulatory network and target genes - TF regulatory network. Hub genes were validated. A total of 891 DEGs 448 of these DEGs presented significant up regulated, and the remaining 443 down regulated were obtained. Pathway enrichment analysis indicated that up regulated genes were mainly linked with glutamine degradation/glutamate biosynthesis, while the down regulated genes were involved in melatonin degradation. GO enrichment analyses indicated that up regulated genes were mainly linked with chemical synaptic transmission, while the down regulated genes were involved in regulation of immune system process. hub and target genes were selected from the PPI network, modules, and target genes - miRNA regulatory network and target genes - TF regulatory network namely YWHAZ, GABARAPL1, EZR, CEBPA, HSPB8, TUBB2A and CDK14. The current study sheds light on the molecular mechanisms of sCJD and may provide molecular targets and diagnostic biomarkers for sCJD.

scholarly journals Network pharmacology-based elucidation of the molecular mechanism underlying the anti-migraine effect of Asari Radix et Rhizoma

2021 ◽  
Vol 18 (10) ◽  
pp. 2067-2074
Author(s):  
Yun-Bin Jiang ◽  
Mei Zhong ◽  
Ting Huang ◽  
Zhong-Hua Dai ◽  
Xing-Bao Tao ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Scientific Basis ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Hub Genes ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment ◽  
Tnf Gene

Purpose: To determine the molecular mechanism involved in the anti-migraine effect of Asari Radix et Rhizoma (ARR) using network pharmacology. Methods: The compounds present in ARR were identified through information retrieval from literature and public databases, and were screened based on absorption, distribution, metabolism, excretion and toxicity. Target genes related to the selected compounds and migraine were identified or predicted from public databases. Hub genes in ARR against migraine were identified through analysis of interactions in overlapping genes between compounds and migraine target genes, based on STRING database. Gene enrichment analysis of overlapping genes was performed using Database for Annotation, Visualization and Integrated Discovery. Results: A total of 138 compounds were selected as potential bioactive compounds in ARR. Target genes related to the selected compounds (611 genes) and migraine (278 genes) were obtained, including 71 overlapping genes. The hub genes in the anti-migraine effect of ARR were BDNF, IL6, COMT, APP and TNF. Gene enrichment analysis showed the top 10 biological processes or pathways involved in the mechanism of anti-migraine action of ARR. The tissue source of the overlapping genes was not limited to the brain. The results from gene enrichment analysis revealed that the effect of ARR on migraine was holistic, which is characteristic of traditional Chinese medicines. Conclusion: Network pharmacology has been used to decipher the molecular mechanism involved in the action of ARR against migraine. The results provide a scientific basis for the clinical effect of ARR on migraine.

scholarly journals Exosomal miR-199a-5p Inhibits Tumorigenesis and Angiogenesis by Targeting VEGFA in Osteosarcoma

2021 ◽  
Author(s):  
Lu Zhang ◽  
Hongxin Cao ◽  
Guanghui Gu ◽  
Dehui Hou ◽  
Yunhao You ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Luciferase Reporter ◽  
Pathway Enrichment Analysis ◽  
Osteosarcoma Cell ◽  
Plasma Samples ◽  
Osteosarcoma Cells ◽  
Hub Genes

Abstract Background: Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents. microRNAs have been found to play a vital role in tumor angiogenesis. Here, we investigated the effects of miR-199a-5p on tumor growth and angiogenesis in osteosarcoma. Furthermore, the underlying molecular mechanisms and signaling pathways were explored.Methods: The datasets were extracted from the Gene Expression Omnibus and the differentially expressed miRNAs (DEmiRNAs) were screened out by the GEO2R online platform. The potential target genes were predicted using the miRTarBase database. The predicted target genes were further analyzed by Gene Ontology and pathway enrichment analysis and a regulatory network of DEmiRNAs and their target genes was constructed. In addition, the effects of osteosarcoma cell derived exosomal miR-199a-5p on the proliferation, migration and neovascularization of HUVECs were evaluated by conducting EdU assays, Transwell experiments and tube formation assays. A dual-luciferase reporter assay was performed to detect whether VEGFA was the direct target of miR-199a-5p. Furthermore, in vivo xenograft models were established to further investigate the intrinsic role of miR-199a-5p in osteosarcoma tumorigenesis and angiogenesis. Results: A total of 149 DE-miRNAs were screened out, including 136 upregulated miRNAs and 13 downregulated miRNAs in human osteosarcoma plasma samples compared with normal plasma samples. A total of 1313 target genes of the top three upregulated and downregulated miRNAs were predicted. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and VEGFA. By constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-663a, miR-199a-5p and miR-223-3p. In addition, we found that the expression level of miR-199a-5p in exosomes derived from osteosarcoma cells was remarkably higher than the osteosarcoma cells, and the exosomes derived from osteosarcoma cells were transported to HUVECs. Overexpression of miR-199a-5p could significantly inhibited HUVEC proliferation, migration and neovascularization, whereas downregulation of miR-199a-5p expression exerted the opposite effect. Moreover, the in vivo results verified that overexpression of miR-199a-5p in osteosarcoma cells could suppress the growth and angiogenesis of tumors. Conclusion: Our results demonstrated that miR-199a-5p could be transported from osteosarcoma cells to HUVECs through exosomes, subsequently targeting VEGFA and inhibiting the growth and angiogenesis of osteosarcoma. Therefore, miR-199a-5p may act as a biomarker in the diagnosis and treatment of osteosarcoma.

scholarly journals A Network Pharmacology Approach to Investigating the Mechanism of Sophorae Flavescentis Radix for the Treatment of Lung Cancer

2020 ◽  
Author(s):  
Le Yu ◽  
Kangyao Yuan ◽  
Jian Zhang ◽  
Jingya Zhao ◽  
Shuchen Pei
Keyword(s):  
Lung Cancer ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Bioactive Components ◽  
Akt Signaling Pathway ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Human Cytomegalovirus Infection ◽  
Protein Protein Interaction Network

Abstract In this study, the bioactive components and predictive targets of Sophorae Flavescentis Radix were investigated by network pharmacology analysis, so as to further elucidate its potential biological mechanism in treating lung cancer. The targets corresponding to lung cancer were obtained by OMIM and Genecards. By intersecting with the targets of Sophorae Flavescentis Radix and lung cancer, the Sophorae Flavescentis Radix-lung cancer targets were obtained. Protein-protein interaction network was constructed by an online database STRING and hub genes were screened by Cytoscape 3.7.0 software. ClusterProfiler package was used to analyze Gene ontology (GO) and KEGG enrichment of the targets in R. A total of 45 bioactive components were screened from Sophorae Flavescentis Radix, corresponding to 482 Sophorae Flavescentis Radix targets and 25019 lung cancer targets. According to the GO and KEGG enrichment analysis, Sophorae Flavescentis Radix played a therapeutic role in treating lung cancer via proteoglycans lung cancer, human cytomegalovirus infection, microRNAs in cancer, PI3K-Akt signaling pathway, etc. Seven hub genes (IL6, CASP3, EGFR, VEGFA, MYC, CCND1 and ESR1) were screened by degree algorithm. In a word, the results of this study may provide novel insights into the mechanisms of Sophorae Flavescentis Radix in treatment of lung cancer.

scholarly journals Dissecting the Mechanism of Yuzhi Zhixue Granule on Ovulatory Dysfunctional Uterine Bleeding by Network Pharmacology and Molecular Docking

2020 ◽  
Author(s):  
Jialin Li ◽  
Hua Luo ◽  
Xinkui Liu ◽  
Jingyuan Zhang ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Uterine Bleeding ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Dysfunctional Uterine Bleeding

Abstract Background: Yuzhi Zhixue Granule (YZG)is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.Methods: The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein-protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.Results: The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds.Conclusion: This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

scholarly journals Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jialin Li ◽  
Hua Luo ◽  
Xinkui Liu ◽  
Jingyuan Zhang ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Uterine Bleeding ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Dysfunctional Uterine Bleeding

Abstract Background Yuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG. Methods The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein–protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules. Results The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds. Conclusion This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

scholarly journals In silico Identification of 10 Hub Genes and an miRNA–mRNA Regulatory Network in Acute Kawasaki Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jin Ma ◽  
Huan Gui ◽  
Yunjia Tang ◽  
Yueyue Ding ◽  
Guanghui Qian ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Signaling Pathway ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Unknown Etiology ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Ppi Networks

Kawasaki disease (KD) causes acute systemic vasculitis and has unknown etiology. Since the acute stage of KD is the most relevant, the aim of the present study was to identify hub genes in acute KD by bioinformatics analysis. We also aimed at constructing microRNA (miRNA)–messenger RNA (mRNA) regulatory networks associated with acute KD based on previously identified differentially expressed miRNAs (DE-miRNAs). DE-mRNAs in acute KD patients were screened using the mRNA expression profile data of GSE18606 from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DE-mRNAs were performed with the DAVID database. Target genes of DE-miRNAs were predicted using the miRWalk database and their intersection with DE-mRNAs was obtained. From a protein–protein interaction (PPI) network established by the STRING database, Cytoscape software identified hub genes with the two topological analysis methods maximal clique centrality and Degree algorithm to construct a miRNA-hub gene network. A total of 1,063 DE-mRNAs were identified between acute KD and healthy individuals, 472 upregulated and 591 downregulated. The constructed PPI network with these DE-mRNAs identified 38 hub genes mostly enriched in pathways related to systemic lupus erythematosus, alcoholism, viral carcinogenesis, osteoclast differentiation, adipocytokine signaling pathway and tumor necrosis factor signaling pathway. Target genes were predicted for the up-regulated and down-regulated DE-miRNAs, 10,203, and 5,310, respectively. Subsequently, 355, and 130 overlapping target DE-mRNAs were obtained for upregulated and downregulated DE-miRNAs, respectively. PPI networks with these target DE-mRNAs produced 15 hub genes, six down-regulated and nine upregulated hub genes. Among these, ten genes (ATM, MDC1, CD59, CD177, TRPM2, FCAR, TSPAN14, LILRB2, SIRPA, and STAT3) were identified as hub genes in the PPI network of DE-mRNAs. Finally, we constructed the regulatory network of DE-miRNAs and hub genes, which suggested potential modulation of most hub genes by hsa-miR-4443 and hsa-miR-6510-5p. SP1 was predicted to potentially regulate most of DE-miRNAs. In conclusion, several hub genes are associated with acute KD. An miRNA–mRNA regulatory network potentially relevant for acute KD pathogenesis provides new insights into the underlying molecular mechanisms of acute KD. The latter may contribute to the diagnosis and treatment of acute KD.

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