scholarly journals Identification of Key Genes and miRNA-mRNA Regulatory Pathways in Bronchopulmonary Dysplasia in Preterm Infants by Bioinformatics Methods

2020 ◽  
Author(s):  
Tong Sun ◽  
Haiyang Yu ◽  
Jianhua Fu

Abstract Background: Bronchopulmonary dysplasia (BPD) remains a severe respiratory complication of preterm infants in neonatal intensive care units (NICUs). However, its pathogenesis has been unclear. Bioinformatics analysis, which can help us explore genetic alternations and recognize latent diagnostic biomarkers, has recently promoted the comprehension of the molecular mechanisms underlying disease occurrence and development. Methods: In this study, we identified key genes and miRNA-mRNA regulatory networks in BPD in preterm infants to elucidate the pathogenesis of BPD. We downloaded and analyzed miRNA and gene expression microarray datasets from the Gene Expression Omnibus database (GEO). Differentially expressed miRNA (DEMs) and differentially expressed genes (DEGs) were obtained through NetworkAnalyst. We performed pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery program (DAVID), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then we used the STRING to establish protein–protein interactions and the Cytoscape tool to establish miRNA–mRNA regulatory networks. Results: We identified 19 significant DEMs and 140 and 33 significantly upregulated and downregulated DEGs, respectively. Functional enrichment analysis indicated that significant DEGs were associated with the antigen processing and presentation, and B-cell receptor signaling pathways in BPD. Key DEGs, such as CD19, CD79B, MS4A1, and FCGR2B were selected as hub genes in PPI networks. Conclusions: In this study, we screened out 19 DEMs that might play important roles in the regulatory networks of BPD. Higher expression of miRNAs such as miR-15b-5p, hsa-miR-32-5p, miR-3613-3p, and miR-33a-5p and lower expression of miRNAs such as miR-3960, miR-425-5p, and miR-3202 might be correlated with the process of BPD.

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Dongyang Li ◽  
Xuanyu Hao ◽  
Yongsheng Song

Objective. To identify key microRNAs (miRNAs) and their regulatory networks in prostate cancer.Methods. Four miRNA and three gene expression microarray datasets were downloaded for analysis from Gene Expression Omnibus database. The differentially expressed miRNA and genes were accessed by a GEO2R. Functional and pathway enrichment analyses were performed using the DAVID program. Protein-protein interaction (PPI) and miRNA-mRNA regulatory networks were constructed using the STRING and Cytoscape tool. Moreover, the results and clinical significance were validated in TCGA data.Results. We identified 26 significant DEMs, 633 upregulated DEGs, and 261 downregulated DEGs. Functional enrichment analysis indicated that significant DEGs were related to TGF-beta signaling pathway and TNF signaling pathway in PCa. Key DEGs such as HSPA8, PPP2R1A, CTNNB1, ADCY5, ANXA1, and COL9A2 were found as hub genes in PPI networks. TCGA data supported our results and the miRNAs were correlated with clinical stages and overall survival.Conclusions. We identified 26 miRNAs that may take part in key pathways like TGF-beta and TNF pathways in prostate cancer regulatory networks. MicroRNAs like miR-23b, miR-95, miR-143, and miR-183 can be utilized in assisting the diagnosis and prognosis of prostate cancer as biomarkers. Further experimental studies are required to validate our results.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8831 ◽  
Author(s):  
Xiaojiao Guan ◽  
Yao Yao ◽  
Guangyao Bao ◽  
Yue Wang ◽  
Aimeng Zhang ◽  
...  

Esophageal cancer is a common malignant tumor in the world, and the aim of this study was to screen key genes related to the development of esophageal cancer using a variety of bioinformatics analysis tools and analyze their biological functions. The data of esophageal squamous cell carcinoma from the Gene Expression Omnibus (GEO) were selected as the research object, processed and analyzed to screen differentially expressed microRNAs (miRNAs) and differential methylation genes. The competing endogenous RNAs (ceRNAs) interaction network of differentially expressed genes was constructed by bioinformatics tools DAVID, String, and Cytoscape. Biofunctional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of the screened genes and the survival of the patients were verified. By analyzing GSE59973 and GSE114110, we found three down-regulated and nine up-regulated miRNAs. The gene expression matrix of GSE120356 was calculated by Pearson correlation coefficient, and the 11696 pairs of ceRNA relation were determined. In the ceRNA network, 643 lncRNAs and 147 mRNAs showed methylation difference. Functional enrichment analysis showed that these differentially expressed genes were mainly concentrated in the FoxO signaling pathway and were involved in the corresponding cascade of calcineurin. By analyzing the clinical data in The Cancer Genome Atlas (TCGA) database, it was found that four lncRNAs had an important impact on the survival and prognosis of esophageal carcinoma patients. QRT-PCR was also conducted to identify the expression of the key lncRNAs (RNF217-AS1, HCP5, ZFPM2-AS1 and HCG22) in ESCC samples. The selected key genes can provide theoretical guidance for further research on the molecular mechanism of esophageal carcinoma and the screening of molecular markers.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1037.2-1038
Author(s):  
X. Sun ◽  
S. X. Zhang ◽  
S. Song ◽  
T. Kong ◽  
C. Zheng ◽  
...  

Background:Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both, and also has a strong genetic predisposition and autoimmune pathogenic traits1. The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. And it’s also a chronic relapsing disease, which often necessitates a long-term therapy2.Objectives:To investigate the molecular mechanisms of psoriasis and find the potential gene targets for diagnosis and treating psoriasis.Methods:Total 334 gene expression data of patients with psoriasis research (GSE13355 GSE14905 and GSE30999) were obtained from the Gene Expression Omnibus database. After data preprocessing and screening of differentially expressed genes (DEGs) by R software. Online toll Metascape3 was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Interactions of proteins encoded by DEGs were discovered by Protein-protein interaction network (PPI) using STRING online software. Cytoscape software was utilized to visualize PPI and the degree of each DEGs was obtained by analyzing the topological structure of the PPI network.Results:A total of 611 DEGs were found to be differentially expressed in psoriasis. GO analysis revealed that up-regulated DEGs were mostly associated with defense and response to external stimulus while down-regulated DEGs were mostly associated with metabolism and synthesis of lipids. KEGG enrichment analysis suggested they were mainly enriched in IL-17 signaling, Toll-like receptor signaling and PPAR signaling pathways, Cytokine-cytokine receptor interaction and lipid metabolism. In addition, top 9 key genes (CXCL10, OASL, IFIT1, IFIT3, RSAD2, MX1, OAS1, IFI44 and OAS2) were identified through Cytoscape.Conclusion:DEGs of psoriasis may play an essential role in disease development and may be potential pathogeneses of psoriasis.References:[1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31].[2]Zhang YJ, Sun YZ, Gao XH, et al. Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis. Mol Med Rep 2019;20(1):225-35. doi: 10.3892/mmr.2019.10241 [published Online First: 2019/05/23].[3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared


2021 ◽  
Author(s):  
Shaowei Fan ◽  
Yuanhui Hu

Abstract Background: Heart failure (HF) is the most common potential cause of death, causing a huge health and economic burden all over the world. So far, some impressive progress has been made in the study of pathogenesis. However, the underlying molecular mechanisms leading to this disease remain to be fully elucidated. Methods: The microarray data sets of GSE76701, GSE21610 and GSE8331 were retrieved from the gene expression comprehensive database (GEO). After merging all microarray data and adjusting batch effects, differentially expressed genes (DEG) were determined. Functional enrichment analysis was performed based on Gene Ontology (GO) resources, Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, gene set enrichment analysis (GSEA), response pathway database and Disease Ontology (DO). Protein protein interaction (PPI) network was constructed using string database. Combined with the above important bioinformatics information, the potential key genes were selected. The comparative toxicological genomics database (CTD) is used to explore the interaction between potential key genes and HF. Results: We identified 38 patients with heart failure and 16 normal controls. There were 315 DEGs among HF samples, including 278 up-regulated genes and 37 down-regulated genes. Pathway enrichment analysis showed that most DEGs were significantly enriched in BMP signal pathway, transmembrane receptor protein serine / threonine kinase signal pathway, extracellular matrix, basement membrane, glycosaminoglycan binding, sulfur compound binding and so on. Similarly, GSEA enrichment analysis showed that DEGs were mainly enriched in extracellular matrix and extracellular matrix related proteins. BBS9, CHRD, BMP4, MYH6, NPPA and CCL5 are central genes in PPI networks and modules. Conclusions: the enrichment pathway of DEGs and go ontology may reveal the molecular mechanism of HF. Among them, target genes EIF1AY, RPS4Y1, USP9Y, KDM5D, DDX3Y, NPPA, HBB, TSIX, LOC28556 and XIST are expected to become new targets for heart failure. Our findings provide potential biomarkers or therapeutic targets for the further study of heart failure and contribute to the development of advanced prediction, diagnosis and treatment strategies.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Haoran Jia ◽  
Zibo Zhang ◽  
Ehsan Sadeghnezhad ◽  
Qianqian Pang ◽  
Shangyun Li ◽  
...  

Abstract Background Grape buds and leaves are directly associated with the physiology and metabolic activities of the plant, which is monitored by epigenetic modifications induced by environment and endogenous factors. Methylation is one of the epigenetic regulators that could be involved in DNA levels and affect gene expression in response to stimuli. Therefore, changes of gene expression profile in leaves and bud through inhibitors of DNA methylation provide a deep understanding of epigenetic effects in regulatory networks. Results In this study, we carried out a transcriptome analysis of ‘Kyoho’ buds and leaves under 5-azacytidine (5-azaC) exposure and screened a large number of differentially expressed genes (DEGs). GO and KEGG annotations showed that they are mainly involved in photosynthesis, flavonoid synthesis, glutathione metabolism, and other metabolic processes. Functional enrichment analysis also provided a holistic perspective on the transcriptome profile when 5-azaC bound to methyltransferase and induced demethylation. Enrichment analysis of transcription factors (TFs) also showed that the MYB, C2H2, and bHLH families are involved in the regulation of responsive genes under epigenetic changes. Furthermore, hormone-related genes have also undergone significant changes, especially gibberellin (GA) and abscisic acid (ABA)-related genes that responded to bud germination. We also used protein-protein interaction network to determine hub proteins in response to demethylation. Conclusions These findings provide new insights into the establishment of molecular regulatory networks according to how methylation as an epigenetic modification alters transcriptome patterns in bud and leaves of grape.


2020 ◽  
Vol 9 (2) ◽  
pp. LMT30
Author(s):  
Chuanli Ren ◽  
Weixiu Sun ◽  
Xu Lian ◽  
Chongxu Han

Aim: To screen and identify key genes related to the development of smoking-induced lung adenocarcinoma (LUAD). Materials & methods: We obtained data from the GEO chip dataset GSE31210. The differentially expressed genes were screened by GEO2R. The protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape. Finally, core genes were screened. The overall survival time of patients with the core genes was analyzed by Kaplan–Meier method. Gene ontology and Kyoto encyclopedia of genes and genomes bioaccumulation was calculated by DAVID. Results: Functional enrichment analysis indicated that nine key genes were actively involved in the biological process of smoking-related LUAD. Conclusion: 23 core genes and nine key genes among them were correlated with adverse prognosis of LUAD induced by smoking.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10529
Author(s):  
Yueqi Li ◽  
Wudi Wei ◽  
Sanqi An ◽  
Junjun Jiang ◽  
Jinhao He ◽  
...  

Background Competitive endogenous RNA (ceRNA) reveals new mechanisms for interactions between RNAs, which have been considered to play a significant role in pathogen-host innate immune response. However, knowledge of ceRNA regulatory networks in Talaromyces marneffei (TM)-macrophages is still limited. Methods Next-generation sequencing technology (NGS) was used to obtain mRNA, miRNA and lncRNA expression profiles in TM-infected macrophages. The R package DESeq2 was used to identify differentially expressed lncRNA, miRNA and mRNA. The R package GOseq was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the ceRNA network of lncRNA–miRNA–mRNA interaction was constructed in Cytoscape. Similarly, functional enrichment analysis on mRNA in the ceRNA network. Finally, two mRNAs and four lncRNAs in the ceRNA network were randomly selected to verify the expression using qRT-PCR. Results In total, 119 lncRNAs, 28 miRNAs and 208 mRNAs were identified as differentially expressed RNAs in TM-infected macrophages. The constructed ceRNA network contains 38 lncRNAs, 10 miRNAs and 45 mRNAs. GO and KEGG analysis of mRNA in the ceRNA network indicated that activated pathways in TM-infected macrophages were related to immunity, inflammation and metabolism. The quantitative validation of the expression of four randomly selected differentially expressed lncRNAs, AC006252.1, AC090197.1, IL6R-AS1, LINC02009 and two mRNAs, CSF1, NR4A3 showed that the expression levels were consistent with those in the RNA-sequencing. Conclusions The ceRNA network related to immunity, inflammation and metabolism plays an important role in TM-macrophage interaction. This study may provide effective and novel insights for further understanding the underlying mechanism of TM infection.


2021 ◽  
Vol 8 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Donghua Zou ◽  
Ling Huang ◽  
...  

Background: To explore the association of DNA methylation and gene expression in the pathology of obesity.Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects. (2) Functional enrichment analysis and construction of differential methylation gene regulatory networks were performed. (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray dataset. (4) Correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNAs matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes—s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interesting different expression positions [differentially methylated positions (DMPs)] and their corresponding gene expression, we found that methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expressions in obese subjects were validated in a separate microarray dataset.Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng Zhang ◽  
Bingye Zhang ◽  
Di Meng ◽  
Chunlin Ge

Abstract Background The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis. Methods The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database. Results We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA. Conclusions Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.


2022 ◽  
pp. 1-12
Author(s):  
Zhengfei Ma ◽  
Ping Zhong ◽  
Peidong Yue ◽  
Zhongwu Sun

<b><i>Background:</i></b> Intracranial aneurysm (IA) is a serious cerebrovascular disease. The identification of key regulatory genes can provide research directions for early diagnosis and treatment of IA. <b><i>Methods:</i></b> Initially, the miRNA and mRNA data were downloaded from the Gene Expression Omnibus database. Subsequently, the limma package in R was used to screen for differentially expressed genes. In order to investigate the function of the differentially expressed genes, a functional enrichment analysis was performed. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to identify the hub module and hub miRNAs. The correlations between miRNAs and mRNAs were assessed by constructing miRNA-mRNA regulatory networks. In addition, in vitro validation was performed. Finally, diagnostic analysis and electronic expression verification were performed on the GSE122897 dataset. <b><i>Results:</i></b> In the present study, 955 differentially expressed mRNAs (DEmRNAs, 480 with increased and 475 with decreased expression) and 46 differentially expressed miRNAs (DEmiRNAs, 36 with increased and 10 with decreased expression) were identified. WGCNA demonstrated that the yellow module was the hub module. Moreover, 16 hub miRNAs were identified. A total of 1,124 negatively regulated miRNA-mRNA relationship pairs were identified. Functional analysis demonstrated that DEmRNAs in the targeted network were enriched in vascular smooth muscle contraction and focal adhesion pathways. In addition, the area under the curve of 16 hub miRNAs was &#x3e;0.8. It is implied that 16 hub miRNAs may be used as potential diagnostic biomarkers of IA. <b><i>Conclusion:</i></b> Hub miRNAs and key signaling pathways were identified by bioinformatics analysis. This evidence lays the foundation for understanding the underlying molecular mechanisms of IA and provided potential therapeutic targets for the treatment of this disease.


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