scholarly journals Identification of Pivotal MicroRNAs and Target Genes Associated with Persistent Atrial Fibrillation Based on Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shengjue Xiao ◽  
Yufei Zhou ◽  
Qiaozhi Liu ◽  
TianTian Zhang ◽  
Defeng Pan
Keyword(s):  
Atrial Fibrillation ◽  
Regulatory Network ◽  
Gene Network ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Expression Array ◽  
Transcription Factor Target

Atrial fibrillation (AF) is one of the most common supraventricular arrhythmias worldwide. However, the specific molecular mechanism underlying AF remains unclear. Our study is aimed at identifying pivotal microRNAs (miRNAs) and targeting genes associated with persistent AF (pAF) using bioinformatics analysis. Three gene expression array datasets (GSE31821, GSE41177, and GSE79768) and an miRNA expression array dataset (GSE68475) associated with pAF were downloaded. Differentially expressed genes (DEGs) were identified using the LIMMA package, and differentially expressed miRNAs (DEMs) were screened from GSE68475. Target genes for DEMs were predicted using the miRTarBase database, and intersections between these target genes and DEGs were selected for further analysis, including the generation of protein–protein interaction (PPI) network, miRNA–transcription factor–target regulatory network, and drug–gene network. A total of 264 DEGs and 40 DEMs were identified between the pAF and control groups. Functional and pathway enrichment analyses of up- and downregulated DEGs were performed. The common genes (CGs) were primarily enriched in the phosphoinositide 3-kinase- (PI3K-) protein kinase B (Akt) signaling pathway, negative regulation of cell division, and response to hypoxia. The PPI network, miRNA–transcription factor–target regulatory network, and drug–gene network were constructed using Cytoscape. The present study revealed several novel miRNAs and genes involved in pAF. We speculated that miR-4298, miR-3125, miR-4306, and miR-671-5p could represent significant miRNAs that act on the target gene superoxide dismutase 2 (SOD2) during the development of pAF and may serve as essential biomarkers for pAF diagnosis and treatment. Moreover, MYC might function in pAF pathogenesis through the PI3K–Akt signaling pathway.

scholarly journals Identifying Pivotal microRNAs and Target Genes Associated With the Pathogenesis of Atrial Fibrillation

2020 ◽  
Author(s):  
Shengjue Xiao ◽  
Yufei Zhou ◽  
Qiaozhi Liu ◽  
Tiantian Zhang ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Signaling Pathway ◽  
Target Genes ◽  
Heat Shock Protein 90 ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Expression Array ◽  
Class B ◽  
Transcription Factor Target ◽  
Limma Package

Abstract Background: Atrial fibrillation (AF) is the most common arrhythmia. However, specific molecular mechanism of AF remains unclear. Our study aimed to identify pivotal target genes and miRNAs in the process of AF, which help provide the basis for clinical diagnosis and the methods for early intervention. Methods: Three gene expression array datasets (GSE31821, GSE41177 and GSE79768) and a miRNA expression array dataset of AF dataset (GSE68475) were downloaded. Differential expressed genes (DEGs) were identified using the LIMMA package and differential expressed miRNAs (DEMs) were screened from GSE68475. Target genes of DEMs were predicted using the miRTarbase database, the number of the intersection between DEGs and these target genes was 26, named CDEGs. The common DEGs (CDEGs) was subject to following analysis. Results: A total of 264 DEGs and 40 DEMs were identified between the AF and control groups. Functional and pathway enrichment analyses of up-regulated DEGs and down-regulated DEGs were performed. The CDEGs were mainly enriched in PI3K-Akt signaling pathway, negative regulation of cell division and response to hypoxia. Subsequently, the protein-protein interaction (PPI) network, the microRNA‐transcription factor‐target regulatory network and drug‐gene network were also constructed by Cytoscape software. Conclusion: The present study revealed several novel genes and miRNAs involved in AF. We speculated that PI3K-Akt signaling pathway might participate in the pathogenesis of AF with the interaction of MYC proto-oncogene (MYC), heat shock protein 90 kDA alpha, class B, member 1 (HSP90AB1) and DNA damage-inducible transcript 4 (DDIT4), moreover, SOD2 (superoxide dismutase 2) could target miR-671-5p, miR-4306, miR-3125, miR-4298 in the progression of AF.

scholarly journals Identification of Potential Biomarkers and Biological Pathways in Juvenile Dermatomyositis Based on miRNA-mRNA Network

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Cheng-Cheng Qiu ◽  
Qi-Sheng Su ◽  
Shang-Yong Zhu ◽  
Ruo-Chuan Liu
Keyword(s):  
Regulatory Network ◽  
Messenger Rna ◽  
Target Genes ◽  
Juvenile Dermatomyositis ◽  
Type I Diabetes ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Type I ◽  
Ppi Network ◽  
Potential Biomarkers

Objective. The aim of this study is to explore the potential pathogenesis of juvenile dermatomyositis by bioinformatics analysis of gene chips, which would screen the hub genes, identify potential biomarkers, and reveal the development mechanism of juvenile dermatomyositis. Material and Methods. We retrieved juvenile dermatomyositis’s original expression microarray data of message RNAs (mRNAs) and microRNAs (miRNAs) from NCBI’s Gene Expression Omnibus database (GEO, http://www.ncbi.nlm.nih.gov/geo/); through the R package of limma in Bioconductor, we can screen the differentially expressed miRNAs and mRNAs, and then we further analyzed the predicted target genes by the methods such as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and miRNA-mRNA regulatory network construction and protein-protein interaction (PPI) network using Cytoscape 3.6.1. Results. Compared with normal juvenile skin tissues, 6 upregulated microRNAs and 5 downregulated microRNAs were identified from 166 downregulated microRNAs and 58 upregulated microRNAs in juvenile dermatomyositis tissues. The enrichment pathways of differentially expressed microRNAs include cell adhesion molecules (CAMs), autoimmune thyroid disease, Type I diabetes mellitus, antigen and presentation, viral myocardium, graft-versus-host disease, and Kaposi sarcoma-associated herpes virus infection. By screening of microRNA-messenger RNA regulatory network and construction of PPI network map, three target miRNAs were identified, namely, miR-193b, miR-199b-5p, and miR-665. Conclusion. We identified mir-193b, mir-199b-5p, and mir-6653 target miRNAs by exploring the miRNA-mRNA regulation network mechanism related to the pathogenesis of juvenile dermatomyositis, which will be of great significance for further study on the pathogenesis and targeted therapy of juvenile dermatomyositis.

scholarly journals Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Dan Wang ◽  
Mingyue Li ◽  
Jing Li ◽  
Xuechao Wan ◽  
Yan Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cancer Progression ◽  
Regulatory Network ◽  
Bioinformatics Analysis ◽  
Mapk Signaling ◽  
Ppi Network ◽  
Network Analyses ◽  
Comprehensive Characterization ◽  
Upstream Regulators

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.

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 Midkine promotes glioblastoma progression via PI3K-Akt signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Beiquan Hu ◽  
Chao Qin ◽  
Li Li ◽  
Lei Wei ◽  
Xianlun Mo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Lines ◽  
Regulatory Network ◽  
Poor Prognosis ◽  
Transcriptional Regulatory Network ◽  
Akt Signaling ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Aberrant Expression

Abstract Background Our previous bioinformatics-based study found that midkine (MDK) was associated with poor prognosis of glioblastoma (GBM). However, the mechanism of MDK in GBM remains elusive. Methods A public GBM-related dataset and GBM tissues from our center were used validate the aberrant expression of MDK in GBM at the RNA and protein levels. The relationship between MDK expression and survival of GBM patients was also explored through survival analysis. Subsequently, we identified MDK-related GBM-specific genes using differential expression analysis. Functional enrichment analyses were performed to reveal their potential biological functions. CCK-8, 5-ethynyl-2′-deoxyuridine, and Matrigel-transwell assays were performed in GBM cell lines in which MDK was knocked out or overexpressed in order assess the effects of MDK on proliferation, migration, and invasion of GBM cells. Western blotting was performed to detect candidate proteins. Results Our study showed MDK is a promising diagnostic and prognostic biomarker for GBM because it is highly expressed in the disease and it is associated with poor prognosis. MDK is involved in various cancer-related pathways, such as PI3K-Akt signaling, the cell cycle, and VEGF signaling. A comprehensive transcriptional regulatory network was constructed to show the potential pathways through which MDK may be involved in GBM. In vitro, Overexpression of MDK augmented proliferation, migration, and invasion of GBM cell lines, whereas suppression of MDK led to the opposite effects. Furthermore, our study confirmed that MDK promotes the progression of GBM by activating the PI3K-Akt signaling pathway. Conclusions Our present study proposes that MDK promotes GBM by activating the PI3K-Akt signaling pathway, and it describes a potential regulatory network involved.

scholarly journals Analysis of microRNA Expression after Glutamine Intervention in Acute Renal Ischemia-Reperfusion Injury

2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Suhua Li ◽  
Xuan Huang ◽  
Shun Wang ◽  
Xueqian Chu ◽  
Munire Aierken
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Kidney Tissue ◽  
Akt Signaling ◽  
Protective Mechanism ◽  
Renal Tubules ◽  
Akt Signaling Pathway

Background. Ischemia-reperfusion acute kidney injury (I/R AKI) is a severe kidney disease with high mortality and morbidity. This study aimed to explore the protective mechanism of glutamine (GLN) against I/R AKI. Methods.The I/R AKI rat model was established, and HE staining of kidney tissue and serum creatinine (SCr) and blood urea nitrogen (BUN) detection were performed. The miRNAs were sequenced by high throughput in rat kidney tissue samples. Differentially expressed miRNAs (DEmiRs) between the I/R group and I/R + GLN group were screened, and enrichment analysis for target genes of DEmiRs was performed. Meanwhile, human HK-2 cells were cultured, and an I/R model was established to verify the expression of DEmiRs. Results. Compared with the I/R group, the SCr and BUN levels at each time point were lower in the I/R + GLN group. Vacuolar degeneration of renal tubules in the I/R + GLN group was significantly reduced. In the 104 DEmiRs, we selected miR-132-5p, miR-205, and miR-615 as key miRNAs. KEGG analysis showed that the Notch signaling pathway, PI3K-Akt signaling pathway, and cGMP signaling pathway were mainly related to the GLN against I/R. qRT-PCR verified the downregulation of miR-205 in the I/R group, compared to the sham and I/R + GLN group. The I/R model was established with HK-2 cells, and the expression of miR-132-5p and miR-205 was decreased. Conclusion. GLN reduced I/R-induced AKI. There were significant differences between miRNAs expression in I/R after GLN treatment. The process of GLN against I/R-induced AKI may be related to the Notch and PI3K-Akt signaling pathway.

scholarly journals Exploring the mechanism of Astragalus membranaceus against uterine fibroids based on network pharmacology

2021 ◽  
Author(s):  
qiu tiantian ◽  
Li DongHua ◽  
Liu Yu ◽  
Gao LiFang ◽  
Wei Chao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Mechanism Of Action ◽  
Regulatory Network ◽  
Drug Targets ◽  
Target Genes ◽  
Uterine Fibroids ◽  
Network Pharmacology ◽  
Ppi Network

Abstract Backgroud: Uterine fibroids (ULs) are the most common benign tumors of the reproductive tract in gynecology and their clinical presentations include menorrhagia, pelvic pressure, dysmenorrhea, and anemia. Surgical resection and the hormonal drug administration are the primary treatment. The plant Astragalus membranaceus (astragalus) has a long history of use in traditional Chinese medicine and studies have shown that it has antitumor effects. However, the role and mechanism of astragalus in ULs are not completely clear. The present study aimed to investigate the astragalus mechanism of action against ULs based on network pharmacology approach, in order to provid insights for the development of a safe and effective drug for the ULs treatment.Methods: The astragalus active ingredients and the potential drug targets were screened by the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform (TCMSP). The gene expression profiles of ULs were obtained from Gene Expression Omnibus (GEO). The intersection of astragalus components target genes and differentially expressed genes between UL and normal patients were obtained using Perl software to provide the astragalus-ULs drug regulatory network. The protein–protein interaction (PPI) network was established using the STRING online database and Cytoscape software, followed by the topological properties analysis of the PPI networks. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were conducted by R software. The KEGG relational network was constructed using Cytoscape software. Results: A total of 21 astragalus active ingredients and 406 drug targets were obtained from the TCMSP. Seventeen of these targets overlap with ULs disease targets and were considered potential targets for the ULs treatment by astragalus. The analysis of the regulatory network showed that the astragalus active components with the most targets are quercetin, kaempferol, mangiferin, tetrodotoxin and isorhamnetin. Target genes with the highest Dgree values obtained from the PPI network analysis are estrogen receptor 1 (ESR1), tumor suppressor factor p53 (TP53), neurotrophic tyrosine kinase receptor 1 (NTRK1) and E3 ubiquitin ligase protein (CUL3). GO and KEGG enrichment analyses indicate that these targets are mainly involved in biological processes related to cellular response to reactive oxygen species, oxidative stress and response to lipopolysaccharides. The main signal transduction pathways involved include the IL-17 and TNF signaling pathways, the AGE-RAGE signaling pathway in diabetic complications and proteoglycans in cancer.Conclusions: The present study demonstrates that the astragalus therapeutic use against ULs have multicomponent and multi-target properties, providing a novel approach to further investigate the astragalus mechanism of action in the treatment of ULs.

scholarly journals MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

2018 ◽  
Vol 50 (6) ◽  
pp. 2365-2389 ◽  
Author(s):  
Ying  Liu ◽  
Yi Miao ◽  
Xin Gao ◽  
Yuan-Yuan Wang ◽  
Huan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Bioinformatics Analysis ◽  
Airway Remodeling ◽  
Akt Signaling ◽  
Airway Smooth Muscle Cells ◽  
Akt Signaling Pathway ◽  
Tgf Β1

Background/Aims: The etiology of asthma, which is a complicated disorder with various symptoms, including wheezing, coughing, and airflow obstruction, remains poorly understood. In addition, the effects of microRNAs (miRs) have not been explored. This study explored the effect of microRNA-200a (miR-200a) on airway smooth muscle cells (ASMCs) and airway remodeling in asthmatic mice. Furthermore, we speculated that miR-200a achieves its effect by targeting FOXC1 via the PI3K/AKT signaling pathway based on differentially expressed gene screening, target miR predictions and a bioinformatics analysis. Methods: Eighty mice were assigned to a saline group or an ovalbumin (OVA) group, and the OVA group was transfected with a series of inhibitors, activators, and siRNAs to test the established mouse model. Airway reactivity and the ratio of eosinophils (EOSs) to leukocytes were detected. An ELISA was adopted to measure the levels of interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor (TNF)-α, and immunoglobulin E (IgE). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1, TGF-β1 and p-AKT in ASMCs. Finally, CCK-8 assays were performed to detect cell proliferation and flow cytometry to detect apoptosis and cell cycle entry. Results: The bioinformatics analysis indicated that miR-200a mediated the PI3K/AKT signaling pathway by targeting FOXC1. In addition, mouse models of asthma were established. An elevated expression of miR-200a, a decreased mRNA and protein expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1 and TGF-β1, a decreased expression of p-AKT, suppressed cell proliferation, accelerated apoptosis, and an increased number of cells at the G0/G1 phase were observed following the upregulation of miR-200a and downregulation of FOXC1. Conclusion: The overexpression of miR-200a may downregulate FOXC1, thereby inhibiting the activation of the PI3K/AKT signaling pathway and ultimately suppressing ASMC proliferation and airway remodeling in asthmatic mice. This evidence supports the potential that miR-200a represents a new approach to treating asthma.

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