Abstract:
BACKGROUND:The recent discovery of cancer/tissue specificity of miRNA has indicated its great potential as a therapeutic target. In Epstein-Barr virus-associated gastric cancer (EBVaGC), host genes are affected by extensive DNA methylation, including miRNAs. However, the role of methylated miRNA in the development of EBVaGC and immune cell infiltration has largely remained elusive. RESULTS:After crossmatching the DNA methylation and expression profile of miRNA and mRNA in the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas Research Network (TCGA), we discovered that miR-129-2-3p was significantly suppressed due to hypermethylation on its enhancer in EBVaGC. The differentially expressed genes (DEGs) added up to 30, among which AKAP12 and LARP6 were predicted to be the target genes of miR-129-2-3p and negatively correlated with patients' survival. Accordingly, miR-129-2-3p was significantly down-regulated in tumor samples in 26 (65%) out of 40 cases in our cohort (P < 0.0001). The proliferation, migration and invasion functions of GC cells were significantly promoted when transfected with miR-129-2-3p inhibitor and suppressed when transfected with mimics or treated with 5-aza-2'-deoxycytidine. Moreover, a comprehensive regulation network was established by combining the putative transcription factors, miRNA-mRNA and protein-protein interaction (PPI) analysis. Pathway enrichment analysis showed that cytokine activity, especially CCL20, was the most prominent biological process in EBVaGC development. Immune cell infiltration analysis demonstrated CD4+ T cell, macrophage and dendritic cell infiltrates were significantly enriched for the prognostic-indicated hub genes. CONCLUSION:This study has provided a comprehensive analysis of differentially expressed miRNAs and mRNAs associated with genome-wide DNA methylation by integrating multi-source data including transcriptome, methylome and clinical data from GEO and TCGA, QPCR of tumor samples and cell function assays. It also gives a hint on the relationships between methylated miRNA, DEGs and the immune infiltration. Further experimental and clinical investigations are warranted to explore the underlying mechanism and validate our findings.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Zhu M,Liang Q,Chen T,Kong Q,Ye G,Yu S,Li X,He Q,Liu H,Hu Y,Yu J,Li Gdoi
10.1186/s13148-020-00989-0subject
Has Abstractpub_date
2021-01-29 00:00:00pages
22issue
1eissn
1868-7075issn
1868-7083pii
10.1186/s13148-020-00989-0journal_volume
13pub_type
杂志文章abstract:BACKGROUND:Mitochondrial dysregulation and aberrant epigenetic mechanisms have been frequently reported in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and several researchers suggested that epigenetic dysregulation in mitochondrial DNA (mtDNA) could contribute to the neurodegenerative pro...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00933-2
更新日期:2020-09-11 00:00:00
abstract:BACKGROUND:Characteristic DNA methylation differences have been identified between primary and metastatic melanomas at EBF3 and/or TBC1D16 gene loci. To further evaluate whether these epigenetic changes may act more generally as drivers of tumour onset and metastasis, we have investigated DNA methylation changes involv...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0710-5
更新日期:2019-08-05 00:00:00
abstract:BACKGROUND:Zinc-finger protein 471 (ZNF471) is a member of the Krüppel-associated box domain zinc finger protein (KRAB-ZFP) family. ZNF471 is methylated in squamous cell carcinomas of tongue, stomach and esophageal. However, its role in breast carcinogenesis remains elusive. Here, we studied its expression, functions, ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00959-6
更新日期:2020-11-17 00:00:00
abstract:BACKGROUND:Normal-weight polycystic ovary syndrome (PCOS) women exhibit adipose resistance in vivo accompanied by enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with accelerated lipid accumulation per cell in vitro. The present study examines chromatin accessibility, RNA expressi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00970-x
更新日期:2020-11-23 00:00:00
abstract:BACKGROUND:Compared to healthy individuals, those with stably repressed HIV experience a higher risk of developing insulin resistance, a hallmark of pre-diabetes and a major determinant for cardiometabolic diseases. Although epigenetic processes, including in particular DNA methylation, appear to be dysregulated in ind...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0694-1
更新日期:2019-06-28 00:00:00
abstract:: Lower than normal levels of oxygen (hypoxia) is a hallmark of all solid tumours rendering them frequently resistant to both radiotherapy and chemotherapy regimes. Furthermore, tumour hypoxia and activation of the hypoxia inducible factor (HIF) transcriptional pathway is associated with poorer prognosis. Driven by bot...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-3-9
更新日期:2011-12-05 00:00:00
abstract:BACKGROUND:Insufficient specificity of the high-risk human papillomavirus (hrHPV) assay in primary cervical cancer screening results in unnecessary referral. Additional assays to triage hrHPV-positive women are needed to improve molecular cervical cancer screening. DNA methylation is a promising biomarker in cervical c...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0122-0
更新日期:2015-08-21 00:00:00
abstract::Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychos...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0038-2
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients. Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2 (FOXA2) re...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0341-7
更新日期:2017-04-24 00:00:00
abstract:BACKGROUND:In vitro follicle culture (IFC), as applied in the mouse system, allows the growth and maturation of a large number of immature preantral follicles to become mature and competent oocytes. In the human oncofertility clinic, there is increasing interest in developing this technique as an alternative to ovarian...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0794-y
更新日期:2019-12-19 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a multisystemic disorder that affects 1:5000 boys. The severity of the phenotype varies dependent on the mutation site in the DMD gene and the resultant dystrophin expression profile. In skeletal muscle, dystrophin loss is associated with the disintegration of myofibers and their i...
journal_title:Clinical epigenetics
pub_type: 杂志文章,评审
doi:10.1186/s13148-021-01001-z
更新日期:2021-01-19 00:00:00
abstract:BACKGROUND:Kawasaki disease (KD) is a prevalent pediatric disease worldwide and can cause coronary artery aneurysm as a severe complication. Typically, DNA methylation is thought to repress the expression of nearby genes. However, the cases in which DNA methylation promotes gene expression have been reported. In additi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0557-1
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). Subjects with FASD show significant neurological deficits, ranging from microencephaly, neurobehavioral, and mental heal...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0416-5
更新日期:2017-10-23 00:00:00
abstract::[This corrects the article DOI: 10.1186/s13148-016-0190-9.]. ...
journal_title:Clinical epigenetics
pub_type: 已发布勘误
doi:10.1186/s13148-016-0250-1
更新日期:2016-08-04 00:00:00
abstract:BACKGROUND:Adiponectin critically contributes to metabolic homeostasis, especially by insulin-sensitizing action. Gestational diabetes mellitus (GDM) is characterized by insulin resistance leading to materno-fetal hyperglycemia and detrimental birth outcomes. By investigating paired subcutaneous (SAT) and visceral adip...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0567-z
更新日期:2018-10-24 00:00:00
abstract:BACKGROUND:Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0335-5
更新日期:2017-04-14 00:00:00
abstract:Background:Maternal social environmental stressors during pregnancy are associated with adverse birth and child developmental outcomes, and epigenetics has been proposed as a possible mechanism for such relationships. Methods:In a Mexican-American birth cohort of 241 maternal-infant pairs, cord blood samples were meas...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0494-z
更新日期:2018-05-08 00:00:00
abstract:BACKGROUND:Prostate cancer (PC) is a commonly diagnosed malignancy in males, especially in the western hemisphere. The extensive use of multiple biomarkers plays an important role in the diagnosis and prognosis of PC. However, the accuracy of biomarkers for PC prognosis needs to be urgently improved. This study aimed t...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0693-2
更新日期:2019-07-09 00:00:00
abstract:BACKGROUND:Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory di...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0561-5
更新日期:2018-11-06 00:00:00
abstract:BACKGROUND:Identifying subjects with a high risk of ischemic stroke is fundamental for prevention of the disease. Both genetic and environmental risk factors contribute to ischemic stroke, but the underlying epigenetic mechanisms which mediate genetic and environmental risk effects are not fully understood. The aim of ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0784-0
更新日期:2019-12-10 00:00:00
abstract:BACKGROUND:About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We theref...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0161-6
更新日期:2015-12-12 00:00:00
abstract:BACKGROUND:Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic hea...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0558-0
更新日期:2018-10-20 00:00:00
abstract:BACKGROUND:Modification of DNA by methylation of cytosines at CpG dinucleotides is a widespread phenomenon that leads to changes in gene expression, thereby influencing and regulating many biological processes. Recent technical advances in the genome-wide determination of single-base DNA-methylation enabled epigenome-w...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-014-0040-6
更新日期:2015-01-22 00:00:00
abstract:Background:This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. Methods:A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0432-5
更新日期:2017-12-20 00:00:00
abstract:: Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases, in which pathology arises from the deleterious consequences of the inheritance of a tandem repeat array whose repeat...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-4-2
更新日期:2012-01-30 00:00:00
abstract:BACKGROUND:Recent developments in genomic sequencing have advanced our understanding of the mutations underlying human malignancy. Melanoma is a prototype of an aggressive, genetically heterogeneous cancer notorious for its biologic plasticity and predilection towards developing resistance to targeted therapies. Eviden...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0091-3
更新日期:2015-06-09 00:00:00
abstract::The study of DNA methylation in development and disease has 'exploded' as a field in recent years, with three major classes of measurement now routine. These encompass (i) locus-specific, (ii) genome-scale/wide and (iii) 'global' methylation approaches. Measures of global methylation refer to the level of 5-methylcyto...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0311-0
更新日期:2017-01-13 00:00:00
abstract::Remodeling of the sperm epigenome by lifestyle factors before conception could account for altered metabolism in the next generation offspring. Here, we hypothesized that endurance training changes the epigenome of human spermatozoa. Using small RNA (sRNA) sequencing and reduced representation bisulfite sequencing (RR...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0446-7
更新日期:2018-01-25 00:00:00
abstract::Altered DNA methylation events contribute to the pathogenesis and progression of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Investigations of global DNA methylation patterns in liver biopsies representing severe NAFLD fibrosis have been limited. We used the HumanMethylation 450K BeadChip ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0525-9
更新日期:2018-07-13 00:00:00
abstract:BACKGROUNDS:Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizz...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00875-9
更新日期:2020-06-09 00:00:00