DNA Methylation Regulates Gene Expression in Intracranial Aneurysms

Yu, Lanbing; Jia, Wang; Wang, Shuo; Zhang, Dong; Zhao, Yuanli; Wang, Rong; Zhao, Jizong

doi:10.1016/j.wneu.2017.04.064

Cited by 30 publications

(31 citation statements)

References 23 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combined with DNA methyltransferases analysis (DNMT1, DNMT3A and DMNT3B), we found NEURL1B High group obviously co-occured with higher expression of DNMT3A and DNMT3B, which promoted us to understand the downregulated expression of NEURL1B in CC. In line with our finding was a reported mechanisms that the DNA methylation have a notable influences on gene expression [ 28 ]. Besides, inspired by the positive correlation between differently methylated sites and prognosis of CC patients, as well as the associations between NEURL1B methylation and clinical stages, suggesting that this epigenetic modification might be a potentially increased risk of colon cancer-related death.…”

Section: Discussionsupporting

confidence: 93%

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Liu

Zhang

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background Aberrant methylation and miRNA-target-gene regulation function as important mechanisms for gene inactivation in colon carcinogenesis. Although a serious of molecular events (such as aberrant alterations of genomics and epigenetics) have been identified to be related to prognostic in colon cancer (CC) patients, beneficial biomarkers for early diagnosis and prognostic evaluation remain largely unknown. Methods In our study, the role of NEURL1B, including gene expression analysis, methylation characteristic, miRNA-target regulation, diagnostic and prognostic significance, were evaculated using multiple bioinformatic tools based on TCGA database and clinical samples. Results Our data showed that NEURL1B was aberrantly downregulated in CC, regardless of the mRNA level or protein level. Moreover, ROC curve and multivariate Cox regression analysis demonstrated that NEURL1B was a diagnostic and independent prognostic facter for CC patients. Of interest, methylation of NEURL1B was also high and closely associated with poor survival in CC. In addition, multiple NEURL1B-target miRNAs were found to be overexpressed in CC tissues. Thus, our findings suggested that NEURL1B participated in the pathological processes of CC as a tumor suppressor gene. Double management, including DNA methylation modification and miRNA-target regulation, were considered to be related to the downregulation of NEURL1B. Importantly, there existing be an significant intersection between miRNAs-target pathways and NEURL1B-target pathways, suggesting that miR-17 and miR-27a might promote tumor cell malignant property by targeting NEURL1B degradation via the activation of PI3K/AKT signaling pathway. Conclusions Taking together, the first investigation of NEURL1B in CC provide us a strong evidences that it might be served as a potential biomarkers for early diagnosis and prognostic evaluation in CC.

show abstract

Section: Discussionsupporting

confidence: 93%

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Liu

Zhang

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…This is evidenced by gene expression studies of human aneurysmal tissues, which found increased matrix degradation processes, inflammatory processes, and production of inflammatory cytokines and chemoattractant proteins in the IA wall [ 8 , 9 ]. Furthermore, Yu et al found that differences in DNA methylation in aneurysmal tissue act to promote inflammatory signaling through the NF-KB, JNK-STAT, and ERK/JNK pathways [ 44 ], uncovering a potential epigenetic underpinning to dysregulated inflammation during IA.…”

Section: Discussionmentioning

confidence: 99%

Circulating neutrophil transcriptome may reveal intracranial aneurysm signature

et al. 2018

View full text Add to dashboard Cite

BackgroundUnruptured intracranial aneurysms (IAs) are typically asymptomatic and undetected except for incidental discovery on imaging. Blood-based diagnostic biomarkers could lead to improvements in IA management. This exploratory study examined circulating neutrophils to determine whether they carry RNA expression signatures of IAs.MethodsBlood samples were collected from patients receiving cerebral angiography. Eleven samples were collected from patients with IAs and 11 from patients without IAs as controls. Samples from the two groups were paired based on demographics and comorbidities. RNA was extracted from isolated neutrophils and subjected to next-generation RNA sequencing to obtain differential expressions for identification of an IA-associated signature. Bioinformatics analyses, including gene set enrichment analysis and Ingenuity Pathway Analysis, were used to investigate the biological function of all differentially expressed transcripts.ResultsTranscriptome profiling identified 258 differentially expressed transcripts in patients with and without IAs. Expression differences were consistent with peripheral neutrophil activation. An IA-associated RNA expression signature was identified in 82 transcripts (p<0.05, fold-change ≥2). This signature was able to separate patients with and without IAs on hierarchical clustering. Furthermore, in an independent, unpaired, replication cohort of patients with IAs (n = 5) and controls (n = 5), the 82 transcripts separated 9 of 10 patients into their respective groups.ConclusionPreliminary findings show that RNA expression from circulating neutrophils carries an IA-associated signature. These findings highlight a potential to use predictive biomarkers from peripheral blood samples to identify patients with IAs.

show abstract

“…As in other complex multigenic conditions, such as autoimmune disease or cancer, there may be a prominent role for epigenetic changes governing the pathophysiology of vasculature remodeling and IA formation risk. 71,75 In addition, although this study was oriented toward identifying putative genes in risk loci, it is possible that modifier alleles in intergenic regions may harbor regulatory elements that are of functional significance. 39 Finally, our study specifically did not encompass analyses of gene expression.…”

Section: Discussionmentioning

confidence: 99%

Genetic basis of intracranial aneurysm formation and rupture: clinical implications in the postgenomic era

Samuel

Radovanović

2019

Neurosurgical Focus

View full text Add to dashboard Cite

OBJECTIVEDespite the prevalence and impact of intracranial aneurysms (IAs), the molecular basis of their pathogenesis remains largely unknown. Moreover, there is a dearth of clinically validated biomarkers to efficiently screen patients with IAs and prognosticate risk for rupture. The aim of this study was to survey the literature to systematically identify the spectrum of genetic aberrations that have been identified in IA formation and risk of rupture.METHODSA literature search was performed using the Medical Subject Headings (MeSH) system of databases including PubMed, EMBASE, and Google Scholar. Relevant studies that reported on genetic analyses of IAs, rupture risk, and long-term outcomes were included in the qualitative analysis.RESULTSA total of 114 studies were reviewed and 65 were included in the qualitative synthesis. There are several well-established mendelian syndromes that confer risk to IAs, with variable frequency. Linkage analyses, genome-wide association studies, candidate gene studies, and exome sequencing identify several recurrent polymorphic variants at candidate loci, and genes associated with the risk of aneurysm formation and rupture, including ANRIL (CDKN2B-AS1, 9p21), ARGHEF17 (11q13), ELN (7q11), SERPINA3 (14q32), and SOX17 (8q11). In addition, polymorphisms in eNOS/NOS3 (7q36) may serve as predictive markers for outcomes following intracranial aneurysm rupture. Genetic aberrations identified to date converge on posited molecular mechanisms involved in vascular remodeling, with strong implications for an associated immune-mediated inflammatory response.CONCLUSIONSComprehensive studies of IA formation and rupture have identified candidate risk variants and loci; however, further genome-wide analyses are needed to identify high-confidence genetic aberrations. The literature supports a role for several risk loci in aneurysm formation and rupture with putative candidate genes. A thorough understanding of the genetic basis governing risk of IA development and the resultant aneurysmal subarachnoid hemorrhage may aid in screening, clinical management, and risk stratification of these patients, and it may also enable identification of putative mechanisms for future drug development.

show abstract

DNA Methylation Regulates Gene Expression in Intracranial Aneurysms

Cited by 30 publications

References 23 publications

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Circulating neutrophil transcriptome may reveal intracranial aneurysm signature

Genetic basis of intracranial aneurysm formation and rupture: clinical implications in the postgenomic era

Contact Info

Product

Resources

About