Aberrant promoter hypermethylation of the CHFR gene in oral squamous cell carcinomas

Baba, Seiji; Hara, Akira; Kato, Kazúo; Long, Nguyen Khanh; Hatano, Yuichiro; Kimura, Masashi; Okano, Yukio; Yamada, Yasuhiro; Shibata, Toshiyuki

doi:10.3892/or_00000552

Cited by 4 publications

(2 citation statements)

References 30 publications

(35 reference statements)

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“…9 A inativação de genes supressores de tumor é crucial no início do desenvolvimento do carcinoma de cabeça e pescoço. 10,47,48 A metilação do DNA é reconhecida como o mecanismo que causa o silenciamento dos genes supressores do tumor, como p14, p15 e p16, em alguns pacientes com carcinoma. 9,47,49 Outro gene supressor de tumor importante na carcinogênese é o receptor de ácido retinóico (RAR).…”

Section: Fatores Determinantes Das Alterações Epigenéticas Na Doença Periodontalunclassified

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Correlações epigenéticas do câncer de boca e da doença periodontal

Dornelas¹,

Luiz²,

Feyo³

et al. 2021

Clin Lab Res Dent

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O objetivo deste artigo foi revisar a literatura em busca de possíveis inter-relações entre as alterações epigenéticas no câncer e na doença periodontal, alertando sobre uma potencial plausibilidade biológica. Para isso, realizou-se uma revisão narrativa da literatura por meio de uma pesquisa nas bases de dados LILACS, PubMed e SciELO pelos descritores “Epigenetic AND Periodontal disease”, “Epigenetic AND Oral cancer”, e “Epigenetic AND Periodontal disease AND Oral cancer”. A partir dessa busca, foram selecionados 56 artigos sobre o tema. As evidências científicas demonstram que a inflamação crônica ocasionada pela presença das bactérias periodontopatogênicas no biofilme dental é capaz de produzir modificações epigenéticas, como metilação do DNA e modificações de histonas. Essas alterações podem inibir genes supressores de tumor e ativar oncogenes, que contribuem para o desenvolvimento e a progressão do câncer de boca. Portanto, há indícios de que o mecanismo fisiopatológico envolvido nas alterações epigenéticas no câncer e na doença periodontal são semelhantes. Conclui-se que existe uma relação positiva entre essas duas doenças, sugerindo que a doença periodontal pode ser um potencial fator de risco para o câncer de boca.

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Section: Fatores Determinantes Das Alterações Epigenéticas Na Doença Periodontalunclassified

“…A taxa de metilação do gene promotor de CHFR é muito menor em mucosas saudáveis que em mucosas com células cancerígenas. 48…”

Section: Fatores Determinantes Das Alterações Epigenéticas Na Doença Periodontalunclassified

Correlações epigenéticas do câncer de boca e da doença periodontal

Dornelas¹,

Luiz²,

Feyo³

et al. 2021

Clin Lab Res Dent

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Regulation of AURKC expression by CpG island methylation in human cancer cells

Fujii

Srivastava²,

Hegde

et al. 2015

Tumor Biol.

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AURKC, a member of the Aurora kinase gene family, is highly expressed in testis but is either moderately expressed or repressed in most somatic cells. Varying expression of AURKC has been observed in human cancers, but the underlying mechanisms of differential expression have been investigated only to a limited extent. We investigated the role of promoter CpG methylation in the regulation of AURKC gene expression in human cancer cells, in relation to a recently reported AURKC transcription repressor PLZF/ZBTB16, implicated in transformation and tumorigenesis. AURKC and PLZF/ZBTB16 expression profiles were investigated in reference to CpG methylation status on the AURKC promoter experimentally, and also in The Cancer Genome Atlas (TCGA) dataset involving multiple cancer types. AURKC promoter showed dense to moderate hypermethylation correlating with low to moderate expression of the gene in normal somatic cells and cancer cell lines, while testis with high expression revealed marked hypo-methylation. Treatment with the demethylating agent, 5-aza-dC, but not the histone deacetylase (HDAC) inhibitor, TSA, led to elevated expression in cancer cell lines, indicating that promoter DNA methylation negatively regulates AURKC expression. High expression of PLZF in PLZF-transfected cells treated with 5-aza-dC only partially repressed expression of AURKC despite 5-aza-dC also inducing elevated PLZF expression. Analyses of the TCGA data showed differential expression of AURKC in multiple cancer types and stronger correlation of AURKC expression with CpG methylation compared to PLZF levels. These findings demonstrate that differential promoter CpG methylation is an important mechanism regulating AURKC expression in cancer cells.

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p16^INK4Aand p14^ARFGene Promoter Hypermethylation as Prognostic Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma: A Review

et al. 2014

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Head and neck squamous cell carcinoma is a heterogeneous group of tumors with each subtype having a distinct histopathological and molecular profile. Most tumors share, to some extent, the same multistep carcinogenic pathways, which include a wide variety of genetic and epigenetic changes. Epigenetic alterations represent all changes in gene expression patterns that do not alter the actual DNA sequence. Recently, it has become clear that silencing of cancer related genes is not exclusively a result of genetic changes such as mutations or deletions, but it can also be regulated on epigenetic level, mostly by means of gene promoter hypermethylation. Results from recent studies have demonstrated that DNA methylation patterns contain tumor-type-specific signatures, which could serve as biomarkers for clinical outcome in the near future. The topic of this review discusses gene promoter hypermethylation in oral and oropharyngeal squamous cell carcinoma (OSCC). The main objective is to analyse the available data on gene promoter hypermethylation of the cell cycle regulatory proteins p16INK4A and p14ARF and to investigate their clinical significance as novel biomarkers in OSCC. Hypermethylation of both genes seems to possess predictive properties for several clinicopathological outcomes. We conclude that the methylation status of p16INK4A is definitely a promising candidate biomarker for predicting clinical outcome of OSCC, especially for recurrence-free survival.

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Aberrant promoter hypermethylation of the CHFR gene in oral squamous cell carcinomas

Cited by 4 publications

References 30 publications

Correlações epigenéticas do câncer de boca e da doença periodontal

Correlações epigenéticas do câncer de boca e da doença periodontal

Regulation of AURKC expression by CpG island methylation in human cancer cells

p16^INK4Aand p14^ARFGene Promoter Hypermethylation as Prognostic Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma: A Review

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Aberrant promoter hypermethylation of the CHFR gene in oral squamous cell carcinomas

Cited by 4 publications

References 30 publications

Correlações epigenéticas do câncer de boca e da doença periodontal

Correlações epigenéticas do câncer de boca e da doença periodontal

Regulation of AURKC expression by CpG island methylation in human cancer cells

p16INK4Aand p14ARFGene Promoter Hypermethylation as Prognostic Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma: A Review

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p16^INK4Aand p14^ARFGene Promoter Hypermethylation as Prognostic Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma: A Review