Abstract:
BACKGROUND:Canine mammary tumor (CMT) has long been considered as a good animal model for human breast cancer (HBC) due to their pathological and biological similarities. However, only a few aspects of the epigenome have been explored in both HBC and CMT. Moreover, DNA methylation studies have mainly been limited to the promoter regions of genes. RESULTS:Genome-wide methylation analysis was performed in CMT and adjacent normal tissues and focused on the intron regions as potential targets for epigenetic regulation. As expected, many tumor suppressors and oncogenes were identified. Of note, most cancer-associated biological processes were enriched in differentially methylated genes (DMGs) that included intron DMRs (differentially methylated regions). Interestingly, two PAX motifs, PAX5 (tumor suppressive) and PAX6 (oncogenic), were frequently found in hyper- and hypomethylated intron DMRs, respectively. Hypermethylation at the PAX5 motifs in the intron regions of CDH5 and LRIG1 genes were found to be anti-correlated with gene expression, while CDH2 and ADAM19 genes harboring hypomethylated PAX6 motifs in their intron region were upregulated. These results were validated from the specimens originally MBD-sequenced as well as additional clinical samples. We also comparatively investigated the intron methylation and downstream gene expression of these genes using human breast invasive carcinoma (BRCA) datasets in TCGA (The Cancer Genome Atlas) public database. Regional alteration of methylation was conserved in the corresponding intron regions and, consequently, gene expression was also altered in HBC. CONCLUSIONS:This study provides good evidence for the conservation of epigenetic regulation in CMT and HBC, and suggests that intronic methylation can be an important factor in better understanding gene regulation in both CMT and HBC.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Nam AR,Lee KH,Hwang HJ,Schabort JJ,An JH,Won SH,Cho JYdoi
10.1186/s13148-020-00888-4subject
Has Abstractpub_date
2020-07-21 00:00:00pages
110issue
1eissn
1868-7075issn
1868-7083pii
10.1186/s13148-020-00888-4journal_volume
12pub_type
杂志文章abstract:BACKGROUND:Epigenome-wide association studies using DNA methylation have the potential to uncover novel biomarkers and mechanisms of cardiovascular disease (CVD) risk. However, the direction of causation for these associations is not always clear, and investigations to-date have often failed to replicate at the level o...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0705-2
更新日期:2019-10-15 00:00:00
abstract:BACKGROUND:Pancreatic cancer has a 5-year survival rate of only 5-7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagn...
journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
doi:10.1186/s13148-016-0286-2
更新日期:2016-11-16 00:00:00
abstract:BACKGROUND:Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next-generation sequencing in representative...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0195-4
更新日期:2016-03-15 00:00:00
abstract:BACKGROUND:Splicing is more efficient when coupled with transcription and it has been proposed that nucleosomes enriched in exons are important for splice site recognition. Lynch syndrome is a familial cancer syndrome that can be caused by the autosomal dominant inheritance of splice site mutations in the MutL homolog ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-014-0032-6
更新日期:2014-12-13 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:Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0152-7
更新日期:2015-11-05 00:00:00
abstract::Lymphocytes from the peripheral blood of patients with prostate cancer-the most frequent (noncutaneous) tumor in men-display epigenetic aberrations (altered modes of allelic replication) characteristic of the malignant phenotype. The present study aims to determine whether replication aberrations add certainty to the ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0029-3
更新日期:2011-08-01 00:00:00
abstract:BACKGROUND:Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which bec...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0377-8
更新日期:2017-08-14 00:00:00
abstract:Background:New efficient therapies for urothelial carcinoma (UC) are urgently required. Small-molecule drugs targeting chromatin regulators are reasonable candidates because these regulators are frequently mutated or deregulated in UC. Indeed, in previous work, Romidepsin, which targets class I histone deacetylases (HD...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0434-3
更新日期:2018-01-04 00:00:00
abstract:BACKGROUND:Human 15q11-13 is responsible for Prader-Willi syndrome (PWS) and Angelman syndrome (AS) and includes several imprinted genes together with bipartite elements named AS-IC (imprinting center) and PWS-IC. These concertedly confer allele specificity on 15q11-13. Here, we report DNA methylation status of 15q11-1...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0633-1
更新日期:2019-02-28 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:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease of the lungs that is currently the fourth leading cause of death worldwide. Genetic factors account for only a small amount of COPD risk, but epigenetic mechanisms, including DNA methylation, have the potential to mediate the interaction...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0464-5
更新日期:2018-03-05 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: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:The mechanism of action of olanzapine in treating schizophrenia is not clear. This research reports the effects of a therapeutic equivalent treatment of olanzapine on DNA methylation in a rat model in vivo.Genome-wide DNA methylation was assessed using a MeDIP-chip analysis. All methylated DNA immunoprecipit...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-6-1
更新日期:2014-01-02 00:00:00
abstract:BACKGROUND:Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that o...
journal_title:Clinical epigenetics
pub_type: 杂志文章,多中心研究
doi:10.1186/s13148-018-0534-8
更新日期:2018-08-29 00:00:00
abstract:BACKGROUND:Preeclampsia is one of the leading causes of fetal and maternal morbidity and mortality worldwide. Preterm babies of mothers with early onset preeclampsia (EOPE) are at higher risks for various diseases later on in life, including cardiovascular diseases. We hypothesized that genome-wide epigenetic alteratio...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0052-x
更新日期:2015-03-13 00:00:00
abstract::Researchers have begun to examine epigenetic alterations in the placenta, making key advances in understanding the epigenetic regulatory mechanisms of the placenta that define underlying processes of human development and disease. Examining changes in microRNA (miRNA) expression associated with environmental exposures...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0046-2
更新日期:2011-08-01 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: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:BACKGROUND:Chronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00903-8
更新日期:2020-07-27 00:00:00
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:The transcription factor Snail2 is a repressor of E-cadherin expression during carcinogenesis; however, the specific mechanisms involved in this process in human colorectal cancer (CRC) remain largely unknown. METHOD:We checked the expression of Snail2 in several clinical CRC specimens. Then, we established...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0592-y
更新日期:2018-12-12 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:BACKGROUND:The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigen...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0177-6
更新日期:2016-01-28 00:00:00
abstract:BACKGROUND:Testicular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as described in testicular dysgenesis syndrome. Interestingly, numerous studies have reported that the precursor of germ cell cancer, germ cell neopla...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0559-z
更新日期:2018-10-19 00:00:00
abstract:Background:Staging and pathological grading systems are convenient but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Identifying biomarkers for HNSCC that will progress and cause death is a critical research area, particularly if the biomarker can be linked to selection of patient...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0485-0
更新日期:2018-04-11 00:00:00
abstract:BACKGROUND:Apabetalone (RVX-208) is a bromodomain and extraterminal protein inhibitor (BETi) that in phase II trials reduced the relative risk (RR) of major adverse cardiac events (MACE) in patients with cardiovascular disease (CVD) by 44% and in diabetic CVD patients by 57% on top of statins. A phase III trial, BETonM...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0696-z
更新日期:2019-07-12 00:00:00
abstract:BACKGROUND:The pathogenesis of systemic lupus erythematosus (SLE) has not yet been completely elucidated. One of the hallmarks of SLE is the production of autoantibodies by uncontrolled over-activated B cells. Early B cell factor 1 (EBF1) contributes to the development, activation, and proliferation of B cells through ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0063-7
更新日期:2015-03-14 00:00:00
abstract:BACKGROUND:Type 2 diabetes mellitus (T2D) is highly prevalent in Middle-Eastern and North African Arab populations, but the molecular basis for this susceptibility is unknown. Altered DNA methylation levels were reported in insulin-secreting and responding tissues, but whether methylation in accessible tissues such as ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0069-1
更新日期:2015-03-28 00:00:00