Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population

Su, Hui-Juan; Zhang, Yang; Ma, Junling; Li, Jiyou; Pan, Kai; You, Wei‐Cheng

doi:10.1186/s12885-015-1962-x

Cited by 6 publications

(5 citation statements)

References 47 publications

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“…In several diseases, and cancer in particular, chromosomal deletions and amplifications are frequent 15 16 . Consequently, use of single-/low-copy genes for normalization was disfavoured a decade ago 17 , but they are still frequently used 18 19 20 21 22 23 . Here we confirm that use of single-/low-copy genes such as ACTB and COL2A1 can result in doubling and halving of PMR values ( Supplementary Table S4 ) for samples with known aberrations at these loci (ref.…”

Section: Discussionmentioning

confidence: 99%

Experimental factors affecting the robustness of DNA methylation analysis

Pharo

Honne

Vedeld

et al. 2016

Sci Rep

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Diverging methylation frequencies are often reported for the same locus in the same disease, underscoring the need for limiting technical variability in DNA methylation analyses. We have investigated seven likely sources of variability at different steps of bisulfite PCR-based DNA methylation analyses using a fully automated quantitative methylation-specific PCR setup of six gene promoters across 20 colon cancer cell lines. Based on >15,000 individual PCRs, all tested parameters affected the normalized percent of methylated reference (PMR) differences, with a fourfold varying magnitude. Additionally, large variations were observed across the six genes analyzed. The highest variation was seen using single-copy genes as reference for normalization, followed by different amounts of template in the PCR, different amounts of DNA in the bisulfite reaction, and storage of bisulfite converted samples. Finally, when a highly standardized pipeline was repeated, the difference in PMR value for the same assay in the same cell line was on average limited to five (on a 0–100 scale). In conclusion, a standardized pipeline is essential for consistent methylation results, where parameters are kept constant for all samples. Nevertheless, a certain level of variation in methylation values must be expected, underscoring the need for careful interpretation of data.

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Section: Discussionmentioning

confidence: 99%

Experimental factors affecting the robustness of DNA methylation analysis

Pharo

Honne

Vedeld

et al. 2016

Sci Rep

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“…39 DNA methylation of COX2 gene was shown to be reduced in the blood of gastric cancer patients. 40 Also, the level of methylation was seen to be not constant and continuously changing during the hepatocytic progression into hepatocellular carcinoma. That was proposed to be motivated by the silencing of tumour-suppressor genes and the activation of key oncogenes.…”

Section: Discussionmentioning

confidence: 97%

The Clinical Significance of Promoter Methylation of Fluoropyrimidine Metabolizing and Cyclooxygenase Genes in Colorectal Cancer

et al. 2021

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Aims: This study investigated the impact of promoter methylation of flouropyrimidine (FP) metabolizing and cyclooxygenase 2 (COX2) genes on their mRNA expression and on the clinical outcome of colorectal cancer (CRC) patients. Methods: Methylation specific-PCR and real time-PCR of thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and COX2 were performed at baseline and after 3 and 6 months of FP therapy. Pairwise comparisons were conducted between the subgroups of CRC patients. The event free survival (EFS) and the hazard of progression were estimated by univariate and multivariate analyses. Results: At baseline CRC patients, both TS and TP were overexpressed, in spite of the unmethylation of TS and the full methylation of TP genes. Significant downexpression of DPD and COX2 were associated their promoter’s methylation. At the end of FP therapy, TS, DPD and COX2 were overexpressed by 7.52, 2.88 and 3.45 folds, respectively, while TP was downexpressed by 0.54 fold. However, no change was observed in the methylation status of genes with FP therapy. Pairwise comparisons revealed significant difference in the expression and the methylation status of genes according to the clinicopathological characters of CRC patients either at baseline or after FP therapy. The overexpression of DPD and COX2 genes were indicators for a poor EFS of CRC patients. Also, the high level of COX2 expression was found to be significantly correlated with the hazard of progression (HR = 1.73, 95% CI = 1.02-3.03). Conclusion: The promoter methylation of FP metabolizing and COX2 genes has significant impact on the expression and the treatment outcome of CRC patients.

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“…To date, miRNAs have been demonstrated as a useful regulator in the development of some tumors, including cell growth, apoptosis, differentiation, invasiveness and migration, and usually serve as a kind of tumor suppressors [7][8][9][10][11]. It has been reported that the COX-2 expression can be found to be increased in a wide variety of tumors, such as human colorectal cancer, liver cancer, cervical cancer, and pancreatic cancer [16][17][18][19]. Some studies indicated that the expression of COX-2 has been thought as a useful tumor biomarker, and COX-2 exhibited the increased invasion potential in cancers.…”

Section: Discussionmentioning

confidence: 99%

MiR-26b suppresses cell proliferation and invasion by targeting cyclooxygenase 2 in human glioblastoma

Jiang¹,

Liu²,

Zhang³

et al. 2016

Oncotarget

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MiRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. Aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the expression and molecular mechanisms of COX-2 and miR-26b in human GBM tissues and GBM cell lines T98G, U87 and U251. In the present study, we found that expression of miR-26b was markedly downregulated in GBM cell lines and human GBM tissues, compared to matched non-tumor associated tissues. Furthermore, miR-26b expression was inversely proportional to that of COX-2 mRNA and protein. Ectopic expression of miR-26b dramatically reduced the proliferation, colony formation, and proliferation/apoptosis-related proteins in GBM cells. Flow cytometry analysis showed that ectopic expression of miR-26b significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Finally, luciferase reporter assay revealed that miR-26b inhibited the expression of COX-2 by binding to the 3'-UTR of COX-2 in GBM cells. Taken together, our results suggest that miR-26b plays an important role to inhibit the proliferation and invasion of GBM cells, and presents a novel mechanism for direct miR-26bmediated suppression of COX-2 in GBM. Thus, miR-26b/COX-2 may have an important role in treatment of GBM patients.

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Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population

Cited by 6 publications

References 47 publications

Experimental factors affecting the robustness of DNA methylation analysis

Experimental factors affecting the robustness of DNA methylation analysis

The Clinical Significance of Promoter Methylation of Fluoropyrimidine Metabolizing and Cyclooxygenase Genes in Colorectal Cancer

MiR-26b suppresses cell proliferation and invasion by targeting cyclooxygenase 2 in human glioblastoma

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