國家衛生研究院 NHRI:Item 3990099045/7025
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    题名: Epigenetic regulation of the X-linked tumour suppressors BEX1 and LDOC1 in oral squamous cell carcinoma
    作者: Lee, CH;Wong, TS;Chan, JYW;Lu, SC;Lin, P;Cheng, AJ;Chen, YJ;Chang, JSM;Hsiao, SH;Leu, YW;Li, Ci;Hsiao, JR;Chang, JY
    贡献者: National Institute of Cancer Research;Division of Environmental Health and Occupational Medicine
    摘要: 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-kappaB (NF-κB) signaling pathway, which is the most frequently hyperactivated signaling 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.
    日期: 2013-07
    關聯: Journal of Pathology. 2013 Jul;230(3):298-309.
    Link to: http://dx.doi.org/10.1002/path.4173
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-3417&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000320122100008
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84878771970
    显示于类别:[李家惠] 期刊論文
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