DLEC1 is not silenced solely by promoter methylation in head and neck squamous cell carcinoma

Seven, Didem; Yavuz, Elif; Kılıç, Erdem; Baltaci, Elif; Karaman, Emin; Ulutin, Turgut; Buyru, Nur

doi:10.1016/j.gene.2015.03.004

Cited by 8 publications

(7 citation statements)

References 29 publications

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“…-540 to -130 CpG sites +132 to +363 CpG sites expression level was not associated with its degree of methylation was also reported for other genes (29). Methylation in other CpG islands and mechanisms, including histone modifications, small RNA and genetic abnormalities, may be involved (30,31); this involvement requires further investigation.…”

Section: Discussionmentioning

confidence: 71%

Methylation pattern of preferentially expressed antigen of melanoma in acute myeloid leukemia and myelodysplastic syndromes

et al. 2017

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Abstract. Preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is overexpressed in a variety of hematologic malignancies with a great variation in expression. The majority of patients with acute myeloid leukemia (AML) 1-eight-twenty one (ETO) + AML and a certain number of myelodysplastic syndromes (MDS) have an abnormally high increase in PRAME expression level. The landscape of PRAME methylation requires evaluation in order to determine the most relevant sites and the exact association of its methylation with expression level and type of disease. In the present study, bone marrow samples collected from 8 AML1-ETO + AML, 4 MDS, 3 AML1-ETO -AML and 2 normal volunteers underwent bisulfate sequencing to analyze the methylation status of all four 5'-C-phosphate-G-3' (CpG) regions within the entire PRAME gene. The median PRAME transcript level of 15 patients was 204.5% (range, 0.02-710.3%). PRAME transcript levels were inversely associated with the degree of methylation of the -389 to -146 CpG sites (r=-0.69; P=0.002) in the 3' part of the promoter region and the +132 to +363 CpG sites (r=-0.69; P=0.006) in the exon 1b region. However, not every sample strictly followed this correlation: Certain samples with high degrees of methylation demonstrated abnormally high expression levels, and vice versa. The methylation ratios of CpG sites in exon 1a were low for all samples (range, 0.0-13.8%), and those in exon 2 were similar in 16 samples (range, 72.4-93.4%), with the exception of one patient with high expression (425.2%) and significantly low degree of methylation in the PRAME gene (22.2%). MDS patients revealed similar methylation ratios in the 3' section of the promoter region, but tended to have lower methylation ratios in the exon 1b region (P=0.62 and P=0.09, respectively) compared with those observed in AML1-ETO + patients with AML and similar degree of PRAME overexpression. Therefore, the hypomethylation of CpG sites in the 3' part of the promoter region and in exon 1b was typically found with PRAME overexpression in AML and MDS. Methylation of other CpG islands, epigenetic and genetic mechanisms, and type of disease may also be involved.

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Section: Discussionmentioning

confidence: 71%

Methylation pattern of preferentially expressed antigen of melanoma in acute myeloid leukemia and myelodysplastic syndromes

et al. 2017

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“…In addition, aberrant gene methylation is shown to be associated with smoking, a key risk factor for NSCLC 14 . DLEC1 (deleted in lung and esophageal cancer), located on the 3p22-21.3, is a tumor-suppressor gene which plays a role in the cell-cycle control by inducing G1 arrest 15 . Previous studies showed that DLEC1 promoter methylation was associated with downregulation or loss of DLEC1 expression in lung cancer 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological Significance and Diagnostic Value of <i>DLEC1</i> Hypermethylation in Lung Cancer: A Meta-analysis

Mao

Guo

et al. 2019

J Nippon Med Sch

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Background: DLEC1 is a tumor-suppressor gene which plays a role in carcinogenesis. The purpose of the current study was to help establish the diagnostic performance of DLEC1 methylation in lung cancer. Methods: PubMed, Embase, CNKI, and Wanfang databases were searched to obtain eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. The diagnostic value was assessed by the summary receiver operating characteristics test. Results: A total of 7 articles, with 8 studies that included 673 lung cancer and 581 control samples, were collected in this meta-analysis. Our results showed a significant association of DLEC1 hypermethylation with lung cancer (P < 0.00001, OR = 13.93, 95% CI = 9.44-20.55). The frequency of DLEC1 methylation was significantly higher in squamous cell carcinoma (SCC) than adenocarcinoma (AC). Moreover, DLEC1 was more frequently methylated in patients with lung cancer aged 60 years or over, patients with lymphatic metastasis, or patients with stage III/IV lung cancer. In addition, there was a sensitivity value of 0.90 (95% CI = 0.86-0.93) and a specificity value of 0.60 (95% CI = 0.56-0.63), a pooled positivelikelihood ratio (PLR) of 2.27 (95% CI = 2.08-2.48), a pooled negative-likelihood ratio (NLR) of 0.17 (95% CI = 0.12-0.23), a diagnostic odds ratio (DOR) of 14.72 (10.09-21) and an area under the curve (AUC) of 0.8146 using DLEC1 methylation in the prediction of lung cancer risk. Conclusion: This meta-analysis confirms that DLEC1 methylation is a promising biomarker for lung cancer.

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“…On the other hand, in vitro and in vivo experiments have demonstrated that DLEC1 is a tumor suppressor silenced by DNA methylation in a range of common tumors, such as ovarian, hepatocellular, gastric, lung, head and neck, prostate and breast carcinomas (Kwong et al 2006;Qiu et al 2008;Seng et al 2008;Seven et al 2015;Ye et al 2014;Ying et al 2009;Zhang et al 2015). DLEC1 methylation is associated with the AJCC staging of hepatocellular carcinoma (Qiu et al 2008), prostate cancer progression (Zhang et al 2015) and a higher recurrence rate in gastric cancer (Ye et al 2014).…”

Section: Introductionmentioning

confidence: 99%

The pro-survival function of DLEC1 and its protection of cancer cells against 5-FU-induced apoptosis through up-regulation of BCL-XL

et al. 2019

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The tumor suppressor DLEC1 has been shown to promote cell proliferation when AP-2a2 is down-regulated in HCT116 stable clones, suggesting its pro-survival nature. However, the pro-survival function of DLEC1 has not been confirmed in other cells and its underlying mechanisms remain elusive. Therefore, we knocked down DLEC1 in a panel of cell lines and found that DLEC1 depletion caused various extents of cell death through intrinsic pathway. DLEC1 overexpression promoted cell survival and reduced cell death in cancer cells after 5-FU treatment, while DLEC1 down-regulation sensitized cancer cells to 5-FU. Further studies demonstrated that DLEC1 attenuated the increase in cleaved PARP, caspase-3 and caspase-7, the activity of caspase-9 and the diffusion of cytosolic cytochrome c from mitochondria. Our data also showed that BCL-XL was up-regulated by DLEC1 in stable clones after 5-FU treatment. Altogether, these results indicated that DLEC1 protects cells against cell death induced by 5-FU through the attenuation of active proteins in caspase cascade and the up-regulation of BCL-XL. Therefore, DLEC1 can be a pro-survival protein under certain circumstances and a potential therapeutic target for increasing sensitivity of cancer cells to 5-FU.

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DLEC1 is not silenced solely by promoter methylation in head and neck squamous cell carcinoma

Cited by 8 publications

References 29 publications

Methylation pattern of preferentially expressed antigen of melanoma in acute myeloid leukemia and myelodysplastic syndromes

Methylation pattern of preferentially expressed antigen of melanoma in acute myeloid leukemia and myelodysplastic syndromes

Clinicopathological Significance and Diagnostic Value of <i>DLEC1</i> Hypermethylation in Lung Cancer: A Meta-analysis

The pro-survival function of DLEC1 and its protection of cancer cells against 5-FU-induced apoptosis through up-regulation of BCL-XL

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