scholarly journals Combined Analysis of ceRNA Regulatory Network and DNA Methylation in CAD

2021 ◽  
Author(s):  
Yue Zhao ◽  
Chen Wang ◽  
Wangxia Li ◽  
Bingyu Jin ◽  
Yang Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Clinical Samples ◽  
Gene Expressions ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Differentially Methylated Genes

Abstract BackgroundThe mobidity and mortality of coronary artery disease (CAD) is increasing year by year. Hence it is urgent to probe into the molecular mechanism of CAD and seek new therapeutic strategies. The purpose of our study was to screen genes associated with the development of CAD by using bioinformatics tools and clinical samples. MethodsMicroarray datasets from the Gene Expression Omnibus (GEO) database of peripheral blood cells (PBLs) were chosen for this study, and candidate differentially expressed microRNAs (DEMs) were screened using the limma and weighted co-expression network analysis (WGCNA) packages in R (v4.0). Subsequently, we construct a competitive endogenous RNAs (ceRNA) network and perform enrichment analysis of genes in the network. Meanwhile, differentially methylated genes (DMGs) in PBLs were identified using the "ChAMP" package in a DNA methylation chip. We then constructed the methylation-associated ceRNA network in CAD. Eventually, the methylation levels of genes and the relationship with the expression of genes in ceRNA were validated in PBLs samples using the Illumina Methylation 850K chip and transcriptome sequencing, while gene expressions were verified by qRT-PCR. And the regulation of DNA methylation on gene expression was verified in the THP-1 cells treated with 5-Aza-2'-deoxycytidine (5-AZA). ResultsA total of 71 differentially expressed miRNAs were screened by both WGCNA and limma. Then the ceRNA network in CAD was constructed with 269 nodes and 705 edges, which were significantly enriched in the chemokine-mediated signaling pathway and so on. Furthermore, from 4354 identified DMGs in a methylation data, 34 methylation-associated differentially expressed genes (DEGs) and 1 differentially expressed lncRNA (DEL) were obtained. After verification of methylation experiments in study population A, three genes were found to have altered methylation consistent with the bioinformatics results. And these genes were correlated in terms of methylation and expression levels. Corresponding with the bioinformatics results, qRT-PCR results in validation set B also showed that the expression of AGPAT4 and FAM169A were significantly lower in CAD. In addition, 5-AZA treatment could increase the expression of AGPAT4 and FAM169A in THP-1 cells. ConclusionsOur study deepens the understanding of the molecular mechanisms underlying the pathogenesis of CAD and provides new ideas for its treatment.

scholarly journals Intrauterine calorie restriction affects placental DNA methylation and gene expression

2013 ◽  
Vol 45 (14) ◽  
pp. 565-576 ◽  
Author(s):  
Pao-Yang Chen ◽  
Amit Ganguly ◽  
Liudmilla Rubbi ◽  
Luz D. Orozco ◽  
Marco Morselli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chronic Diseases ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Specific Effects ◽  
Differentially Methylated Genes ◽  
Critical Organ ◽  
Successive Generations

Maternal nutrient restriction causes the development of adult onset chronic diseases in the intrauterine growth restricted (IUGR) fetus. Investigations in mice have shown that either protein or calorie restriction during pregnancy leads to glucose intolerance, increased fat mass, and hypercholesterolemia in adult male offspring. Some of these phenotypes are shown to persist in successive generations. The molecular mechanisms underlying IUGR remain unclear. The placenta is a critical organ for mediating changes in the environment and the development of embryos. To shed light on molecular mechanisms that might affect placental responses to differing environments we examined placentas from mice that had been exposed to different diets. We measured gene expression and whole genome DNA methylation in both male and female placentas of mice exposed to either caloric restriction or ad libitum diets. We observed several differentially expressed pathways associated with IUGR phenotypes and, most importantly, a significant decrease in the overall methylation between these groups as well as sex-specific effects that are more pronounced in males. In addition, a set of significantly differentially methylated genes that are enriched for known imprinted genes were identified, suggesting that imprinted loci may be particularly susceptible to diet effects. Lastly, we identified several differentially methylated microRNAs that target genes associated with immunological, metabolic, gastrointestinal, cardiovascular, and neurological chronic diseases, as well as genes responsible for transplacental nutrient transfer and fetal development.

scholarly journals Bioinformatics Analysis Reveals the Potential Diagnostic Biomarkers for Abdominal Aortic Aneurysm

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinsheng Xie ◽  
En ci Wang ◽  
Dandan Xu ◽  
Xiaolong Shu ◽  
Yu fei Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Aortic Aneurysms ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Abdominal Aortic

Objectives: Abdominal aortic aneurysms (AAAs) are associated with high mortality rates. The genes and pathways linked with AAA remain poorly understood. This study aimed to identify key differentially expressed genes (DEGs) linked to the progression of AAA using bioinformatics analysis.Methods: Gene expression profiles of the GSE47472 and GSE57691 datasets were acquired from the Gene Expression Omnibus (GEO) database. These datasets were merged and normalized using the “sva” R package, and DEGs were identified using the limma package in R. The functions of these DEGs were assessed using Cytoscape software. We analyzed the DEGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein–protein interaction networks were assembled using Cytoscape, and crucial genes were identified using the Cytoscape plugin, molecular complex detection. Data from GSE15729 and GSE24342 were also extracted to verify our findings.Results: We found that 120 genes were differentially expressed in AAA. Genes associated with inflammatory responses and nuclear-transcribed mRNA catabolic process were clustered in two gene modules in AAA. The hub genes of the two modules were IL6, RPL21, and RPL7A. The expression levels of IL6 correlated positively with RPL7A and negatively with RPL21. The expression of RPL21 and RPL7A was downregulated, whereas that of IL6 was upregulated in AAA.Conclusions: The expression of RPL21 or RPL7A combined with IL6 has a diagnostic value for AAA. The novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of AAA.

scholarly journals Integrated Analysis of Methylome and Transcriptome Following Developmental Atrazine Exposure in Zebrafish Reveals Aberrant Gene-Specific Methylation of Neuroendocrine and Reproductive Pathways

2020 ◽  
Author(s):  
Chris Bryan ◽  
Li Lin ◽  
Junkai Xie ◽  
Janiel Ahkin Chin Tai ◽  
Katharine A. Horzmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The United States ◽  
Integrated Analysis ◽  
Aberrant Methylation ◽  
Morphological Alterations ◽  
Differentially Methylated Genes ◽  
Genome Bisulfite Sequencing ◽  
Aberrant Gene

ABSTRACTAtrazine (ATZ) is one of the most commonly used herbicides in the United States. Previous studies have hypothesized the role of ATZ as an endocrine disruptor (EDC), and developmental exposure to ATZ has been shown to lead to behavioral and morphological alterations. Specific epigenetic mechanisms responsible for these alterations, however, are yet to be elucidated. In this study, we exposed zebrafish embryos to 0.3, 3, and 30 ppb (µg/L) of ATZ for 72 hours post fertilization. We performed whole-genome bisulfite sequencing (WGBS) to assess the effects of developmental ATZ exposure on DNA methylation in female fish brains. The number of differentially methylated genes (DMG) increase with increasing dose of treatments. DMGs are enriched in neurological pathways with extensive methylation changes consistently observed in neuroendocrine and reproductive pathways. To assess the effects of DNA methylation on gene expression, we integrated our data with transcriptomic data. Four genes, namely CHD9, FRAS1, PID1, and PCLO, were differentially expressed and methylated in each dose. Overall, this study identifies specific genes and pathways with aberrant methylation and expression following ATZ exposure as targets to elucidate the molecular mechanisms of ATZ toxicity and presents ATZ-induced site-specific DNA methylation as a potential mechanism driving aberrant gene expression.

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Regulatory Networks ◽  
Enrichment Analysis ◽  
Microarray Dataset ◽  
Functional Enrichment Analysis ◽  
Normal Subjects ◽  
Functional Enrichment ◽  
Differentially Methylated Genes

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.

scholarly journals Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng Zhang ◽  
Bingye Zhang ◽  
Di Meng ◽  
Chunlin Ge
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Ppi Networks ◽  
Differentially Methylated Genes ◽  
Tumorigenesis And Progression

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.

LSD1 Influences Both Histone and DNA Methylation During Terminal Erythroid Maturation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3671-3671
Author(s):  
Michael Getman ◽  
Jeffrey Malik ◽  
James Palis ◽  
Laurie A Steiner
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Histone Demethylase ◽  
Differentially Expressed ◽  
Enzyme Linked Immunosorbent Assay ◽  
Erythroid Progenitor ◽  
Erythroid Maturation

Abstract The molecular mechanisms that drive the maturation of a committed erythroid progenitor to a functional red blood cell are incompletely understood. LSD1 (Lysine-Specific Histone Demethylase 1) is a widely expressed histone demethylase that plays an important role in erythroid maturation (Kereyni, elife, 2013). Although LSD1 is important for a number of biologic processes ranging from embryonic development to leukemogenesis, the molecular mechanisms underlying the influence of LSD1 on gene expression are incompletely understood. The goal of our study is to elucidate the molecular mechanisms by which LSD1 regulates erythroid gene expression and influences erythroid maturation. We hypothesize that LSD1 promotes specific patterns of histone and DNA methylation that facilitate gene expression changes necessary for normal erythroid maturation to occur. To address this hypothesis, the functional and molecular consequences of LSD1 knockdown were assessed in Extensively Self Renewing Erythroblasts (ESREs), a non-transformed, karyotypically normal model of terminal erythroid maturation (England, Blood, 2011). Primary fetal liver was cultured in the presence of EPO, SCF, IGF1 and dexamethasone to derive ESREs. The ESREs were capable of extensive ex-vivo expansion, doubling daily at the proerythroblast phase, however when matured, >90% of cells became benzidine positive and >65% enucleated within 3 days. Lentiviral-mediated shRNA was used to knock down LSD1 in expanding ESREs. Imaging flow cytometry done on maturation day 3 demonstrated that the knockdown cells had impairments in multiple facets of maturation, with larger cell and nuclear areas, higher kit expression, and lower rates of enucleation than the scramble control. LSD1 knockdown was also associated with impaired hemoglobin accumulation (78% vs. 95% benzidine positive; p<0.005). Treatment of ESREs with an inhibitor to LSD1 (Tranylcypromine; TCP) resulted in similar abnormalities in cell and nuclear size, kit expression, hemoglobin accumulation, and enucleation (40% vehicle vs.1% TCP). The functional deficits in maturation, including abnormal kit expression and low rates of enucleation, persisted on maturation day 4. To delineate the molecular mechanisms underlying this maturation impairment, RNA-seq was done in LSD1 knockdown and scramble control samples, and 230 differentially expressed genes (FDR<0.01) were identified using cuffdiff (Trapnell, Nat Biotech, 2013). Consistent with LSD1’s role in erythroid maturation, Ingenuity Pathway Analysis identified multiple networks involving hemoglobin synthesis, and GATA1, EPO, and KLF1 were all predicted as upstream regulators (p-values of 8.24e10-11, 7.25 e10-6, and 3.86e10-4, respectively). To better understand how LSD1 influences gene expression, chromatin immunoprecipitation coupled with high throughput sequencing was used to identify sites of H3K4me2 binding in the differentially expressed genes. 214/230 differentially expressed genes were associated with sites of H3K4me2 occupancy. Quantitative ChIP demonstrated that LSD1 inhibition was associated with increases in H3K4me2 levels at a subset of these sites, however consistent with previous studies, global levels of H3K4me2, determined by Enzyme Linked Immunosorbent Assay (ELIZA), did not change significantly. Although it is known that LSD1 demethylates and stabilizes the maintenance DNA methyltransferase DNMT1 (Wang, Nat Genet 2009), the consequences of LSD1 loss on DNA methylation (5-methyl cytosine; 5-mC) have yet to be investigated. To gain a comprehensive understanding of how LSD1 regulates erythroid gene expression, changes in the level of 5-mC were assessed after knockdown or inhibition of LSD1. Global 5-mC levels, determined by ELIZA assay, were ∼30% lower in TCP treated samples than vehicle treated control (p<0.02) and western blot demonstrated a 3-fold decrease in DNMT1 protein in the TCP treated samples. Both methyl binding domain pull-down coupled with quantitative PCR and genome-wide bisulfite sequencing were utilized to assess changes in 5-mC levels in the differentially expressed genes. Loss of LSD1 was associated with significantly lower levels of 5-mC at several differentially expressed, erythroid-specific genes, such as bh1. Taken together, these data support the hypothesis that LSD1 influences both histone and DNA methylation at genes important for erythroid maturation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Integrated Analysis of lncRNA-miRNA-mRNA ceRNA Network in Human Diarrhea Irritable Bowel Syndrome

2021 ◽  
Author(s):  
Jun-wei LIANG ◽  
Wen-jun BAI ◽  
Xiao-yan WANG ◽  
Li-li CHI
Keyword(s):  
Irritable Bowel Syndrome ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Down Regulation ◽  
Tissue Samples ◽  
Cerna Network ◽  
Irritable Bowel

Abstract Background:Many studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in diarrhea irritable bowel syndrome (IBS-D) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in IBS-D on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network.Methods:This study collected the mRNAs (GSE36701) expression data within human tissue samples with IBS-D group and normal group based on Gene Expression Omnibus (GEO) database and collected the differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEmiRs) based on PubMed.Functional enrichment analysis of DEGs was performed on the DAVID database. Then the interaction network was constructed and visualized using STRING database and Cytoscape.Results: This study identified 3192 DEmRNAs (1437 with up-regulation and 1755 with down-regulation),29 DEmiRs (18 upregulated and 11 downregulated)and 2 DELs(one upregulated and one downregulated) between IBS-D and control samples.Furthermore,we constructed a lncRNA-miRNA-mRNA network through two DELs (lncRNA TUG1 with up-regulation and lncRNA H19 with down-regulation), four DemiRs (hsa-miR-148a-3p,hsa-miR-342-3p,hsa-miR-149-5p with up-regulation and hsa-miR-219a-5p with down-regulation)and 24 DEGs (4 with up-regulation and 20 with down-regulation) with 42 axes. Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, two critical genes were found (BCL2L11 and QKI). Conclusion:In conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating IBS-D.BCL2L11 axis(LncH19-hsa-miR-148a-3p-BCL2L11) may via interaction with PI3K/AKT pathways in IBS-D.Our results shed more lights on the possible pathogenic mechanism in IBS-D using a lncRNA-associated ceRNA network.

scholarly journals Integrative DNA Methylation and Gene Expression Analysis Reveals Candidate Biomarkers Associated with Dichotomized Response to Chemoimmunotherapy in Diffuse Large B-Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Ellen K. Kendall ◽  
Manishkumar S. Patel ◽  
Sarah Ondrejka ◽  
Agrima Mian ◽  
Yazeed Sawalha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Research Funding ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
B Cell Lymphoma ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Gene Sets

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. While 60% of DLBCL patients achieve complete remission with frontline therapy, relapsed/refractory (R/R) DLBCL patients have a poor prognosis with median overall survival below one year, necessitating investigation into the biological principles that distinguish cured from R/R DLBCL. Recent analyses have identified unfavorable molecular signatures when accounting for gene expression, copy number alterations and mutational profiles in R/R DLBCL. However, an integrative analysis of the relationship between epigenetic and transcriptomic changes has yet to be described. In this study, we compared baseline methylation and gene expression profiles of DLBCL patients with dichotomized clinical outcomes. Methods: Diagnostic DLBCL biopsies were obtained from two patient cohorts: patients who relapsed or were refractory following chemoimmunotherapy ("R/R"), and patients who entered durable clinical remission following therapy ("cured"). The median age for R/R and cured cohorts were 62 (range 35-86) years vs. 64 (range 28-83) years (P= 0.27). High-intermediate or high IPI scores were present in 14 vs. 6 patients (P= 0.08) in the R/R and cured cohorts, respectively. All patients were treated with frontline R-CHOP or R-EPOCH. DNA and RNA were extracted simultaneously from formalin-fixed, paraffin embedded biopsy samples. An Illumina 850k Methylation Array was used to identify DNA methylation levels in 29 R/R patients and 20 cured patients. RNA sequencing was performed on 9 R/R patients and 7 cured patients at diagnosis using Illumina HiSeq4000. Differentially methylated probes were identified using the DMRcate package, and differentially expressed genes were identified using the DESeq2 package. Gene set enrichment analysis was performed using canonical pathway gene sets from MSigDB. Results: At the time of diagnosis, we found significant epigenetic and transcriptomic differences between cured and R/R patients. Comparing cured to R/R samples, there were 8,159 differentially methylated probes (FDR&lt;0.05). Differentially methylated regions between R/R and cured cohorts overlap with genes previously identified as mutation hotspots in DLBCL. Upon comparing transcriptomic profiles between R/R and cured, 267 genes were found to be differentially expressed (Log2FC&gt;|1| and FDR&lt;0.05). Gene set enrichment analysis revealed gene sets related to cell cycle, membrane trafficking, Rho and Rab family GTPase function, and transcriptional regulation were upregulated in the R/R samples. Gene sets related to innate immune signaling, Type I and II interferon signaling, fatty acid and carbohydrate metabolism were upregulated in the cured samples. To identify genes likely to be regulated by specific changes in methylation, we selected genes that were both differentially expressed and differentially methylated between the R/R and cured cohorts. In the R/R samples, 13 genes (ARMC5, ARRDC1, C12orf57, CCSER1, D2HGDH, DUOX2, FAM189B, FKBP2, KLF5, MFSD10, NEK8, NT5C, and WDR18) were significantly hypermethylated and underexpressed when compared to cured specimens, suggesting that epigenetic silencing of these genes is associated with lack of response to chemoimmunotherapy. In contrast, 12 genes (ATP2B1, C15orf41, FAM102B, FAM3C, FHOD3, FYTTD1, GPR180, KIAA1841, LRMP, MEF2A, RRAS2, and TPD52) were significantly hypermethylated and underexpressed in cured patients, suggesting that epigenetic silencing of these genes is favorable for treatment response. Many of these epigenetically modified genes have been previously implicated in cancer biology, including roles in NOTCH signaling, chromosomal instability, and biomarkers of prognosis. Conclusions: This is the first integrative epigenetic and transcriptomic analysis of diagnostic biopsies from cured and R/R DLBCL patients following chemoimmunotherapy. At the time of diagnosis, both the methylation and gene expression profiles significantly differ between patients that enter durable remission as opposed to those who are R/R to therapy. Soon, the hypomethylating agent CC-486 (i.e. oral azacitidine) will be explored in combination with mini-R-CHOP for older DLBCL patients in whom DNA methylation is likely increased. These data support the use of hypomethylating agents to potentially restore sensitivity of DLBCL to chemoimmunotherapy. Disclosures Hsi: Eli Lilly: Research Funding; Abbvie: Research Funding; Miltenyi: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; CytomX: Consultancy, Honoraria. Hill:Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding.

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

2020 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Dong-Hua Zhou ◽  
Ling Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Microarray Data ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Normal Subjects ◽  
Functional Enrichment ◽  
Data Set ◽  
Differentially Methylated Genes

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.

scholarly journals Construction of a circRNA - Mediated ceRNA Network Reveals Novel Biomarkers for Aortic Dissection

2021 ◽  
Author(s):  
De-Bin Liu ◽  
You-Fu He ◽  
Gui-Jian Chen ◽  
Hua Huang ◽  
Xu-Ling Xie ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Arterial Blood

Abstract Background Aortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circular RNAs (circRNAs) play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in aortic dissection based on the circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. Methods Expression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified in AD by bioinformatics analysis. Further bioinformatics analyses, including circRNA-miRNA-mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, were used to predict the potential functions of circRNA-associated ceRNA regulatory network. RNA was isolated from human arterial blood samples after which quantitative real-time PCR (qRT-PCR) was performed to confirm the DERNAs. Results We identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) when AD samples were compared with normal ascending aorta samples (adjusted P-value < 0.05 and | log2FC |> 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix (ECM) receptor interaction signaling pathways. Simultaneously, the present study successfully constructed a ceRNA regulatory network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1) in AD. Furthermore, qRT-PCR demonstrated that hsa_circRNA_082317 andα5 integrin (ITGA5) were significantly up-regulated in AD (n = 3), and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3). The expression of hsa-miR-149-3p target mRNA, ITGA5, was positively modulated by hsa_circRNA_082317. Conclusion This is the first study to demonstrate the circRNA-associated ceRNA regulatory network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression of AD and thus may serve as potential biomarkers for the diagnosis and treatment of AD.

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