scholarly journals Integrated DNA Methylation and Gene Expression Analysis Identified S100A8 and S100A9 in the Pathogenesis of Obesity

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.

2020 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Dong-Hua Zhou ◽  
Ling Huang ◽  
...  

Abstract 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 network were performed; (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray data set; and (4) correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNA 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 interested different expression positions (DMPS) and their corresponding gene expression, we found that the methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expression in obese subjects were validated in a separate microarray data set.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.


2020 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Dong-Hua Zhou ◽  
Ling Huang ◽  
...  

Abstract 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 network were performed; (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray data set; and (4) correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNA 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 interested different expression positions (DMPS) and their corresponding gene expression, we found that the methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expression in obese subjects were validated in a separate microarray data set.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.


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 ◽  
pp. 1-10
Author(s):  
Min Wei ◽  
Sijun Meng ◽  
Sufang Shi ◽  
Lijun Liu ◽  
Xujie Zhou ◽  
...  

<b><i>Introduction:</i></b> Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. It involves both genetic and environmental factors, among which DNA methylation, the most studied epigenetic modification, was shown to play a role. Here, we assessed genome-wide DNA methylation and gene expression profiles in 2 pairs of IgAN-discordant monozygotic (MZ) twins, in order to characterize methylation changes and their potential influences on gene expression in IgAN. <b><i>Methods:</i></b> Genome-wide DNA methylation and gene expression profiles were evaluated in peripheral blood mononuclear cells obtained from 2 IgAN-discordant MZ twins. Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were detected, and an integrated analysis was performed. Finally, functional enrichment analysis was done for DMR-associated genes and DEGs. <b><i>Results:</i></b> Totally 521 DMRs were detected for 2 IgAN-discordant MZ twins. Among them, 9 DMRs were found to be mapped to genes that differentially expressed in 2 MZ twins, indicating the potential regulatory mechanisms of expression for these 9 genes (<i>MNDA</i>, <i>DYSF</i>, <i>IL1R2</i>, <i>TLR6</i>, <i>TREML2</i>, <i>TREM1</i>, <i>IL32</i>, <i>S1PR5</i>, and <i>ADGRE3</i>) in IgAN. Biological process analysis of them showed that they were mostly involved in the immune system process. Functional enrichment analysis of DEGs and DMR-associated genes both identified multiple pathways relevant to inflammatory and immune responses. And DMR-associated genes were significantly enriched in terms related to T-cell function. <b><i>Conclusions:</i></b> Our findings indicate that changes in DNA methylation patterns were involved in the pathogenesis of IgAN. Nine target genes detected in our study may provide new ideas for the exploration of molecular mechanisms of IgAN.


2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Yun Zhong ◽  
Zhe Liu ◽  
Dangchi Li ◽  
Qinyuan Liao ◽  
Jingao Li

Background. An increasing number of studies have indicated that the abnormal expression of certain long noncoding RNAs (lncRNAs) is linked to the overall survival (OS) of patients with myeloma. Methods. Gene expression data of myeloma patients were downloaded from the Gene Expression Omnibus (GEO) database (GSE4581 and GSE57317). Cox regression analysis, Kaplan-Meier, and receiver operating characteristic (ROC) analysis were performed to construct and validate the prediction model. Single sample gene set enrichment (ssGSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to predict the function of a specified lncRNA. Results. In this study, a seven-lncRNA signature was identified and used to construct a risk score system for myeloma prognosis. This system was used to stratify patients with different survival rates in the training set into high-risk and low-risk groups. Test set, the entire test set, the external validation set, and the myeloma subtype achieved the authentication of the results. In addition, functional enrichment analysis indicated that 7 prognostic lncRNAs may be involved in the tumorigenesis of myeloma through cancer-related pathways and biological processes. The results of the immune score showed that IF_I was negatively correlated with the risk score. Compared with the published gene signature, the 7-lncRNA model has a higher C-index (above 0.8). Conclusion. In summary, our data provide evidence that seven lncRNAs could be used as independent biomarkers to predict the prognosis of myeloma, which also indicated that these 7 lncRNAs may be involved in the progression of myeloma.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Guiying Bai ◽  
Chenxuan Wu ◽  
Yingtang Gao ◽  
Guiming Shu

This study has analyzed the gene expression patterns of an IPMN microarray dataset including normal pancreatic ductal tissue (NT), intraductal papillary mucinous adenoma (IPMA), intraductal papillary mucinous carcinoma (IPMC), and invasive ductal carcinoma (IDC) samples. And eight clusters of differentially expressed genes (DEGs) with similar expression pattern were detected byk-means clustering. Then a survey map of functional disorder in IPMN progression was established by functional enrichment analysis of these clusters. In addition, transcription factors (TFs) enrichment analysis was used to detect the key TFs in each cluster of DEGs, and three TFs (FLI1, ERG, and ESR1) were found to significantly regulate DEGs in cluster 1, and expression of these three TFs was validated by qRT-PCR. All these results indicated that these three TFs might play key roles in the early stages of IPMN progression.


Author(s):  
Peigen Chen ◽  
Yingchun Guo ◽  
Lei Jia ◽  
Jing Wan ◽  
TianTian He ◽  
...  

Objective: In this study, we mainly explored two questions: Which microorganisms were functionally active in the endometrium of patients with endometrial cancer (EC)? What kind of response did the human host respond to functionally active microorganisms?Methods: Nine endometrial cancer patients and eight normal subjects were included in this study. HMP Unified Metabolic Analysis Network 3 (HUMAnN3) was used to obtain functional information of microorganisms. In addition, metaCyc-based GSEA functional enrichment analysis was used to obtain information on the metabolic pathways of the human host. At the same time, the O2PLS model and Spearman correlation analysis were used to analyze the microorganisms–host interaction.Results: With the novel metatranscriptome analysis pipeline, we described the composition of more than 5,000 functionally active microorganisms and analyzed the difference in microorganisms between the EC and the normal group. Our research found that these microorganisms were involved in part of the metabolic process of endometrial cancer, such as 6-sulfo-sialyl Lewis x epitope, N-acetyl-beta-glucosaminyl. In addition, the host–microbiota crosstalk of EC endometrium also included many biological processes, mainly functions related to tumor migration and the Apelin signaling pathway.Conclusion: The functionally active microorganisms in the EC endometrium played an essential role in the occurrence and migration of tumors. This meant that functionally active microorganisms could not be ignored in the treatment of endometrial cancer. This study helped to better understand the possible role of endometrial functional, active microorganisms in the occurrence and development of EC in patients with endometrial cancer and provided new information for new attempts to treat EC.


2021 ◽  
Author(s):  
Mohib kakar ◽  
Muhammad Mehboob ◽  
Muhammad Akram ◽  
Imran Iqbal ◽  
Hafza Ijaz ◽  
...  

Abstract Objective The goal of this study was to understand possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Methods GEO contains datasets of gene expression, miRNA and methylation patterns of diseased and healthy/control patients. GSE62232 Dataset was selected by employing the server Gene Expression Omnibus. A total of 91 samples were collected, including 81 HCC samples and 10 healthy samples as control. GSE62232 was analyzed through GEO2R, and Functional Enrichment Analysis was performed to extract rational information from a set of DEGs. The Protein-Protein Relationship Networking search method has been used for extracting genes interacting. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analyzed using GEPIA to estimate the effect of their differential expression on cancer progression. Results We identified the top 10 hub genes through Cytohubba plugin. These genes include Cell Cycle Regulatory Cyclins and Cyclin-dependent proteins CCNA2, CCNB1 and CDK1. The pathogenesis and prognosis of HCC may be directly linked with the aforementioned genes. Conclusion In this analysis, we found critical genes for HCC that showed recommendations for more diagnostic and predictive biomarkers studies that could promote selective molecular therapy for HCC.


2021 ◽  
Author(s):  
Mohib kakar ◽  
Muhammad Mehboob ◽  
Muhammad Akram ◽  
Imran Iqbal ◽  
Hafza Ijaz ◽  
...  

Abstract The goal of this study was to understand possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Gene Expression Omnibus (GEO) contains datasets of gene expression, miRNA and methylation patterns of diseased and healthy/control patients. GSE62232 Dataset was selected by employing the server GEO. A total of 91 samples were collected, including 81 HCC samples and 10 healthy samples as control. GSE62232 was analyzed through GEO2R, and functional enrichment analysis was performed to extract rational information from a set of DEGs. The protein-protein relationship networking search method was used for extracting interacting genes. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analyzed using GEPIA to estimate the effect of their differential expression on cancer progression. We identified the top 10 hub genes through Cytohubba plugin. These genes include cell cycle regulatory cyclins and cyclin-dependent proteins CCNA2, CCNB1 and CDK1. The pathogenesis and prognosis of HCC may be directly linked with the aforementioned genes. In this analysis, we found critical genes for HCC that showed recommendations for more diagnostic and predictive biomarker studies that could promote selective molecular therapy for HCC.


Sign in / Sign up

Export Citation Format

Share Document