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Fernández-Alvarez A, Llorente-Izquierdo C, Mayoral R, et al. Evaluation of epigenetic modulation of cyclooxygenase-2 as a prognostic marker for hepatocellular carcinoma. Oncogenesis. 2012;1:e23doi: 10.1038/oncsis.2012.23.
Fernández-Alvarez, A., Llorente-Izquierdo, C., Mayoral, R., Agra, N., Boscá, L., Casado, M., & Martín-Sanz, P. (2012). Evaluation of epigenetic modulation of cyclooxygenase-2 as a prognostic marker for hepatocellular carcinoma. Oncogenesis, 1e23. https://doi.org/10.1038/oncsis.2012.23
Fernández-Alvarez, A, et al. "Evaluation of epigenetic modulation of cyclooxygenase-2 as a prognostic marker for hepatocellular carcinoma." Oncogenesis vol. 1 (2012): e23. doi: https://doi.org/10.1038/oncsis.2012.23
Fernández-Alvarez A, Llorente-Izquierdo C, Mayoral R, Agra N, Boscá L, Casado M, Martín-Sanz P. Evaluation of epigenetic modulation of cyclooxygenase-2 as a prognostic marker for hepatocellular carcinoma. Oncogenesis. 2012 Jul 09;1:e23. doi: 10.1038/oncsis.2012.23. PMID: 23552739; PMCID: PMC3412654.
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Oncogenesis. 2012 Jul 09;1:e23. doi: 10.1038/oncsis.2012.23.

Evaluation of epigenetic modulation of cyclooxygenase-2 as a prognostic marker for hepatocellular carcinoma.

Oncogenesis

A Fernández-Alvarez, C Llorente-Izquierdo, R Mayoral, N Agra, L Boscá, M Casado, P Martín-Sanz

Affiliations

  1. Instituto de Biomedicina de Valencia, IBV-CSIC, Valencia, Spain.

PMID: 23552739 PMCID: PMC3412654 DOI: 10.1038/oncsis.2012.23

Abstract

Cyclooxygenases (COX-1 and 2) catalyze the first step in prostanoid biosynthesis. They are implicated in homeostatic processes with an important role in inflammation and carcinogenesis. In the liver, COX-2 expression is restricted to proliferation or dedifferentiation situations. The COX-2 promoter contains numerous CpG islands that, when hypermethylated, result in transcriptionally silencing thus regulating the growth of carcinoma cells. In this work, we investigated whether a correlation exists between COX-2 expression and methylation signatures at the 5'region of the gene in hepatoma cell lines and human hepatocellular carcinoma (HCC). We also examined the acetylation status of the COX-2 promoter and the effects of histone deacetylase (HDAC) inhibitors on COX-2 expression. Our results suggest a significant association between reduced COX-2 expression and promoter hypermethylation of COX-2 and histone deacetylation in some hepatoma cell lines and in HCC. Treatment with demethylating agents or HDAC inhibitors restored the expression of COX-2. Moreover, in an HCC cohort, a statistically significant inverse association was observed between COX-2 mRNA levels and promoter methylation. In agreement with these data, a reduction of overall survival of the patients was observed after decreased COX-2 expression by promoter hypermethylation and histone H3 hypoacetylation.

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