DNMT3B Expression Might Contribute to Abnormal Methylation of RASSF1A in Lager Colorectal Adenomatous Polyps

Background. It is pretty well known that DNA methyltransferases (DNMTs) are actively involved in abnormal cell growth. The goal of the current study is to explore the correlation between DNMT expression and colorectal adenomatous polyps (CAPs). Method. Twenty pairs of CAP samples with a diameter≥10 mm and corresponding normal colorectal mucosa (NCM) tissues from patients were used in the present study. The expression levels and activity of DNA methyltransferases (DNMTs) were measured in the CAP tissues. The global methylation and the promoter methylation level of 3 kinds of tumour suppressor gene were detected. Results. mRNA and protein levels of DNMT3B were found to be elevated in the CAP tissues compared with the control tissue. Additionally, the methylation of long interspersed nuclear elements-1 (LINE-1/L1) was decreased in the CAP tissue. Furthermore, methylation of the promoter of a tumour suppressor gene Ras association domain family 1A (RASSF1A) was increased in the CAP tissues, while the mRNA levels of RASSF1A were decreased. Conclusions. These results suggest that the overexpression of DNMT3B may contribute to a role in the genesis of CAPs through the hypomethylation of chromosomes in the whole cell and promoter hypermethylation of RASSF1A.

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Putative tumour-suppressor gene DAB2is frequently down regulated by promoter hypermethylation in nasopharyngeal carcinoma

BMC Cancer ◽

10.1186/1471-2407-10-253 ◽

2010 ◽

Vol 10 (1) ◽

Cited By ~ 52

Author(s):

Joanna H Tong ◽

David C Ng ◽

Shuk L Chau ◽

Ken K So ◽

Patrick P Leung ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Promoter Hypermethylation ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Tumour Suppressor

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Molecular profile of nasopharyngeal carcinoma: analysing tumour suppressor gene promoter hypermethylation by multiplex ligation-dependent probe amplification

Journal of Clinical Pathology ◽

10.1136/jclinpath-2017-204661 ◽

2017 ◽

Vol 71 (4) ◽

pp. 351-359 ◽

Cited By ~ 5

Author(s):

Marc L Ooft ◽

Jolique van Ipenburg ◽

Rob van Loo ◽

Rick de Jong ◽

Cathy Moelans ◽

...

Keyword(s):

Treatment Options ◽

Disease Free Survival ◽

Promoter Hypermethylation ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Tumour Suppressor ◽

Molecular Profile ◽

Tumour Suppressor Genes ◽

Suppressor Genes ◽

Dependent Probe

AimsTo assess differences in methylation profiles, and thus pathogenesis, between Epstein-Barr virus (EBV)-positive and negative nasopharyngeal carcinomas (NPCs). Also, promoter hypermethylation is a common phenomenon in early carcinogenesis to inactivate tumour suppressor genes. Since epigenetic changes are reversible, the therapeutic application of methylation inhibitors could provide treatment options.MethodsWe evaluated promoter hypermethylation profiles of 22 common tumour suppressor genes in 108 NPCs using methylation-specific multiplex ligation-dependent probe amplification. Correlation between methylation, clinicopathological features (including EBV) and survival was examined. Cluster analysis was also performed.ResultsHypermethylation of RASSF1A and ESR1 was significantly more frequent in EBV-positive NPC, while hypermethylation of DAPK1 was more frequent in EBV-negative NPC. In logistic regression, age, with EBV-positive NPC occurring at earlier age, and RASSF1, with RASSF1 hypermethylation being more frequent in EBV-positive NPC, remained significant. In EBV-positive NPC, hypermethylation of RASSF1A predicted worse overall survival (OS) (HR 3.058,95% CI 1.027 to 9.107). In EBV-negative NPC, hypermethylated adenomatous polyposis coli (APC) was a predictor of poor disease-free survival (DFS) (HR 6.868, 95% CI 2.142 to 22.022).ConclusionThere are important epigenetic differences between EBV-negative and EBV-positive NPCs, with EBV-negative NPC having a more similar hypermethylation profile to other head and neck squamous cell carcinomas than EBV-positive NPC. Hypermethylation of RASSF1A might contribute to worse OS in EBV-positive NPC, and may be an important event in the pathogenesis of EBV-infected NPC. Hypermethylation of APC might contribute to worse DFS in EBV-negative NPC.

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DNA damage signalling recruits RREB-1 to the p53 tumour suppressor promoter

Biochemical Journal ◽

10.1042/bj20090342 ◽

2009 ◽

Vol 422 (3) ◽

pp. 543-551 ◽

Cited By ~ 23

Author(s):

Hanshao Liu ◽

Hoi Chin Hew ◽

Zheng-Guang Lu ◽

Tomoko Yamaguchi ◽

Yoshio Miki ◽

...

Keyword(s):

Dna Damage ◽

Target Genes ◽

Core Promoter ◽

Genotoxic Stress ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Tumour Suppressor ◽

Dependent Manner ◽

P53 Expression ◽

Protein Levels

Transcriptional regulation of the p53 tumour suppressor gene plays an important role in the control of the expression of various target genes involved in the DNA damage response. However, the molecular basis of this regulation remains obscure. In the present study we demonstrate that RREB-1 (Ras-responsive-element-binding protein-1) efficiently binds to the p53 promoter via the p53 core promoter element and transactivates p53 expression. Silencing of RREB-1 significantly reduces p53 expression at both the mRNA and the protein levels. Notably, disruption of RREB-1-mediated p53 transcription suppresses the expression of the p53 target genes. We also show that, upon exposure to genotoxic stress, RREB-1 controls apoptosis in a p53-dependent manner. These findings provide evidence that RREB-1 participates in modulating p53 transcription in response to DNA damage.

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