O6-methylguanine-DNA methyltransferase gene coding region polymorphisms and oral cancer risk

Huang, Sung Hsien; Chang, Pei Yang; Liu, Chung Ji; Lin, Ming; Hsia, Kan Tai

doi:10.1111/j.1600-0714.2009.00880.x

Cited by 15 publications

(10 citation statements)

References 37 publications

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“…7E and F), suggesting that betel nut chewing may contribute to the downregulation of Meg-3 and the partial of 14q32.2 miRNAs. Several lines of evidence indicate that hypermethylation may be involved in the pathogenesis of oral cancer associated with betel quid chewing (45,46). Therefore, it is reasonable to suppose that the silencing of the 14q32.2 miRNAs, which would seem to be correlated with Meg-3 promoter hypermethylation, is related to betel quid chewing and might be a significant event in oral carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Downregulated miR329 and miR410 Promote the Proliferation and Invasion of Oral Squamous Cell Carcinoma by Targeting Wnt-7b

et al. 2014

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microRNA (miRNA) dysregulation contributes widely to human cancer but has not been fully assessed in oral cancers. In this study, we conducted a global microarray analysis of miRNA expression in 40 pairs of betel quid-associated oral squamous cell carcinoma (OSCC) specimens and their matched nontumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared with the matched tissue. Among these downregulated miRNAs, 19 miRNAs were found and mapped to the chromosome 14q32.2 miRNA cluster region, which resides within a parentally imprinted region designated as Dlk-Dio3 and known to be important in development and growth. Bioinformatic analysis predicted two miRNAs from the cluster region, miR329 and miR410, which could potentially target Wnt-7b, an activator of the Wnt-b-catenin pathway, thereby attenuating the Wnt-b-catenin signaling pathway in OSCC. Stable ectopic expression of Wnt-7b in OSCC cells overexpressing miR329 or miR410 restored proliferation and invasion capabilities abolished by these miRNA. Combining a demethylation agent and a histone deacetylase inhibitor was sufficient to reexpress miR329, miR410, and Meg3, consistent with epigenetic regulation of these miRNA in human OSCC. Specifically, arecoline, a major betel nut alkaloid, reduced miR329, miR410, and Meg3 gene expression. Overall, our results provide novel molecular insights into how betel quid contributes to oral carcinogenesis through epigenetic silencing of tumor-suppressor miRNA that targets Wnt-b-catenin signaling. Cancer Res; 74(24); 7560-72. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

Downregulated miR329 and miR410 Promote the Proliferation and Invasion of Oral Squamous Cell Carcinoma by Targeting Wnt-7b

et al. 2014

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“…Smoking and betel quid chewing are two of the most important risk factors for oral cancer in Taiwan [19], and DNA hypermethylation has been reported to be related to smoking and betel quid chewing [18,29]. Next, we attempted to determine the effect of arecoline, a major component of betel nut alkaloids, and 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), one of the major components of tobacco, on the expression of miR-30a, miR-379, DNMT3B, ADHFE1, and ALDH1A2.…”

Section: Mir-30a and Mir-379 Involved In Arecoline And Nnk Induced Epmentioning

confidence: 99%

MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer

et al. 2020

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Background: Epigenetic silencing of retinoic acid (RA) signaling-related genes have been linked with the pathogenesis and clinical outcome in oral squamous cell carcinoma (OSCC) carcinogenesis. However, the precise mechanisms underlying the abnormal silencing of RA signaling-related genes in OSCC have not been well investigated. Methods: Using combined analysis of genome-wide gene expression and methylation profile from 40 matched normaltumor pairs of OSCC specimens, we found a set of retinoid signaling related genes are frequently hypermethylated and downregulated in OSCC patient samples, including alcohol dehydrogenase, iron containing 1 (ADHFE1) and aldehyde dehydrogenase 1 family, member A2 (ALDH1A2), which are the important rate-limiting enzymes in synthesis of RA. The expression of ADHFE1 and ALDH1A2 in OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. The binding sites of miR-30a and miR-379 with DNA methyltransferase 3B (DNMT3B) were predicted using a series of bioinformatic tools, and validated using dual luciferase assay and Western blot analyses. The functions of miR-30a, miR-379, and DNMT3B were accessed by growth and colony formation analyses using gain-and loss-of-function approaches. Chromatin immunoprecipitation (ChIP) was performed to explore the molecular mechanisms by arecoline and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) treatment. Results: We demonstrated that deregulated miR-30a and miR-379 could represent a mechanism for the silencing of ADHFE1 and ALDH1A2 in OSCC through targeting DNMT3B. Ectopic expression of miR-30a and miR-379 could induce re-expression of methylation-silenced ADHFE1 and ALDH1A2, and lead to growth inhibition in oral cancer cells. Furthermore, the dysregulation of the miRNAs and DNMT-3B may result from exposure to tobacco smoking and betel quid chewing.

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“…Accumulating evidence has suggested that selected environmental factors, including alcohol, tobacco, UV‐irradiation and folate, might influence the development of various human cancers by inducing epigenetic changes . Some supporting evidence derived from clinical observations included altered DNA methylation in betel quid chewers with oral prelesions and the close association of RASSF1A, p16INK4a epigenetic silencing and O 6 ‐methylquanine DNA methyltransferase polymorphisms with betel quid‐chewing habits in OSCC patients. Inactivation of tumour suppressor genes by promoter hypermethylation is commonly involved in oncogenesis .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic regulation of the X‐linked tumour suppressors BEX1 and LDOC1 in oral squamous cell carcinoma

Lee

Wong

Chan

et al. 2013

The Journal of Pathology

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The strong associations between oral squamous cell carcinoma (OSCC) and dietary habits such as alcohol consumption (A), betel quid chewing (B) and cigarette smoking (C) and its predominance in men have been well documented; however, systemic analysis of OSCC is limited. Our study applied high-throughput screening methods to identify causative epigenetic targets in a cohort of men with ABC-associated OSCC. We identified BEX1 and LDOC1 as two epigenetically silenced X-linked tumour suppressors and demonstrated a functional link between the transcription of BEX1 and LDOC1 and promoter hypermethylation. Methylation of the BEX1 and LDOC1 promoters was associated significantly (p < 0.0001) with OSCC and were detected in 75% (42/56) and 89% (50/56) of the samples, respectively. We observed concordant increases in the methylation of both genes in 71% (40/56) of the tumours, and potent in vitro and in vivo growth inhibitory effects in OSCC cells ectopically expressing BEX1 and/or LDOC1. Restored expression of BEX1 and LDOC1 suppressed the nuclear factor-κB (NF-κB) signalling pathway, which is the most frequently hyperactivated signalling pathway in OSCC. This suppression might result from decreased p50 and p65 expression. These findings suggest that silencing of BEX1 and LDOC1 by promoter hypermethylation might represent a critical event in the molecular pathogenesis of OSCC and account for the oncogenic effects of ABC exposure and the male predominance of OSCC occurrence. Microarray data are available in the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/)

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O6-methylguanine-DNA methyltransferase gene coding region polymorphisms and oral cancer risk

Cited by 15 publications

References 37 publications

Downregulated miR329 and miR410 Promote the Proliferation and Invasion of Oral Squamous Cell Carcinoma by Targeting Wnt-7b

Downregulated miR329 and miR410 Promote the Proliferation and Invasion of Oral Squamous Cell Carcinoma by Targeting Wnt-7b

MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer

Epigenetic regulation of the X‐linked tumour suppressors BEX1 and LDOC1 in oral squamous cell carcinoma

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