Hypertensive epigenetics: from DNA methylation to microRNAs

Wang, J; Gong, Li; Tan, Yi; Hui, Rutai; Wang, Y

doi:10.1038/jhh.2014.132

Cited by 41 publications

(32 citation statements)

References 85 publications

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“…In the current study, we identified that miR-181b-1 was likely to be overexpressed in most miRNA profiling studies and had moderate predictive value for PaCa (SEN of 0.62, SPE of 0.81, and AUC of 0.81). During cancer formation, miRNAs are regulated by epigenetic modifications, such as methylation and histone modifications [50,51]. Interestingly, the negative correlation between miR181b-1 expression and methylation status within the 3.5-kb genomic region upstream of the transcription start site was significant (r=-0.19; p=0.01).…”

Section: Discussionmentioning

confidence: 87%

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Zhang

Pan

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.

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Section: Discussionmentioning

confidence: 87%

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Zhang

Pan

et al. 2018

Cell Physiol Biochem

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“…This provides new ideas and methods for the treatment of different diseases. Previous studies have shown a close relationship between a number of candidate hypertension genes and DNA methylation in the development of hypertension [29], such as 11β-HSD2 [3], ACE [30], NKCC1 [4], and adipocyte determination and differentiation factor-l ( ADD-l ) [31]. In addition, peripheral blood genome-wide DNA methylation levels are significantly altered between patients with hypertension and healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Hypomethylation of the Angiotensin II Type I Receptor (<b><i>AGTR1</i></b>) Gene Along with Environmental Factors Increases the Risk for Essential Hypertension

Lin

et al. 2017

Cardiology

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Objectives: The present study aimed to evaluate the hypertension status of community residents, analyze environmental and epigenetic factors, and propose prevention measures for hypertension. Methods: In our study, different methylation levels were distinguished utilizing melting temperature (T_m) values in both the case and the control group. Multiple logistic regression analysis was used to estimate the risk of having essential hypertension (EH) between hypertensive and nonhypertensive participants. A receiver-operating characteristic curve was used to analyze T_m cutoff levels of methylation. Results: The average DNA T_m was 71.784 with a standard deviation of 0.210. The T_m value of community residents (Fujian, China) was inversely correlated with systolic and diastolic blood pressure. Student t test analysis showed a clear separation in T_m expression levels between the hypertensive and the control group (p < 0.05). The T_m value was lower in the hypertension group than in the normotensive group. Multivariate regression analysis showed that high levels of DNA methylation were a protective factor in hypertension with adjustment of demographic and environmental factors, whereas when the T_m value increased by 0.1 units, the risk of hypertension was reduced by 0.652 times. Patients that smoked and consumed an irregular diet demonstrated a lower degree of methylation in the presence of hypertension. Conclusions: DNA methylation affects the risk for the development of hypertension; therefore, epigenetic markers could be used to measure hypertension levels to help elucidate the pathogenesis of EH.

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“…Due to its stability in blood samples and transmissibility during cell division, DNA methylation can be used to characterize early disease progression, and it provides an efficient way to prevent and predict diseases in clinical practice. To date, changes in DNA methylation have been widely reported to be involved in the onset of a variety of metabolic diseases, including diabetes mellitus, fatty liver, and metabolic syndrome [10-15]. …”

Section: Introductionmentioning

confidence: 99%

Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

Yao¹,

Mo²,

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Metabolic diseases are leading health concerns in today’s global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. Methods: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs). Eight volunteers had PC and 4 had balanced constitutions. Results: Methylation data indicated a genome-scale hyper-methylation pattern in PC. We located 288 differentially methylated probes (DMPs). A total of 256 genes were mapped, and some of these were metabolic-related. SQSTM1, DLGAP2 and DAB1 indicated diabetes mellitus; HOXC4 and SMPD3, obesity; and GRWD1 and ATP10A, insulin resistance. According to Ingenuity Pathway Analysis (IPA), differentially methylated genes were abundant in multiple metabolic pathways. Conclusion: Our results suggest the potential risk for metabolic disorders in individuals with PC. We also explain the clinical characteristics of PC with DNA methylation features.

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Hypertensive epigenetics: from DNA methylation to microRNAs

Cited by 41 publications

References 85 publications

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Hypomethylation of the Angiotensin II Type I Receptor (<b><i>AGTR1</i></b>) Gene Along with Environmental Factors Increases the Risk for Essential Hypertension

Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

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