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粘蛋白:上皮癌中一个新的表观遗传生物标志物家族。

Mucins: a new family of epigenetic biomarkers in epithelial cancers.

作者信息

Van Seuningen Isabelle, Vincent Audrey

机构信息

Inserm, U837, Jean-Pierre Aubert Research Center, Team 5 Epithelial Differentiation and Carcinogenesis, Place de Verdun, 59045 Lille cedex, France +33 320 29 88 67 ; +33 320 53 85 62 ;

出版信息

Expert Opin Med Diagn. 2009 Jul;3(4):411-27. doi: 10.1517/17530050902852697. Epub 2009 May 2.

Abstract

BACKGROUND

Epigenetic regulation of gene expression is a common feature of cancer development and progression. The search for new biomarkers and tools to detect cancer in its early stages has unveiled the usefulness of epigenetics and genes epigenetically regulated as potential targets. Among them, genes encoding mucins have been shown to be regulated by DNA methylation and histone modifications in epithelial cancer cells. These genes encode either secreted glycoproteins necessary for epithelial homeostasis or membrane-bound glycoproteins that participate in tumor progression.

OBJECTIVE

The important biological functions played by these large molecules in pathophysiology of the epithelia make them key genes to target to propose new therapeutic strategies and new diagnostic and/or prognostic tools in cancer.

RESULTS

In that context, the recent data regarding the epigenetic regulation of these genes are reported and their potential as biomarkers in cancer is discussed. Mucin genes are also potentially interesting to study as they may be regulated by miRNAs but also regulate miRNA activity.

CONCLUSION

Epigenetic regulation of mucin genes is at its dawn, but there is great potential in that research to (with new technologies and high-throughput methods) provide quickly new biomarkers (diagnostic and/or prognostic), help tumor identification/classification and propose new therapeutic targets to the clinician and pathologist.

摘要

背景

基因表达的表观遗传调控是癌症发生和发展的一个共同特征。寻找早期检测癌症的新生物标志物和工具揭示了表观遗传学以及受表观遗传调控的基因作为潜在靶点的有用性。其中,编码黏蛋白的基因已被证明在上皮癌细胞中受DNA甲基化和组蛋白修饰的调控。这些基因要么编码上皮细胞稳态所需的分泌型糖蛋白,要么编码参与肿瘤进展的膜结合糖蛋白。

目的

这些大分子在上皮细胞病理生理学中发挥的重要生物学功能使其成为提出癌症新治疗策略以及新诊断和/或预后工具的关键靶向基因。

结果

在此背景下,报告了有关这些基因表观遗传调控的最新数据,并讨论了它们作为癌症生物标志物的潜力。黏蛋白基因也可能是值得研究的对象,因为它们可能受微小RNA(miRNA)调控,同时也调控miRNA活性。

结论

黏蛋白基因的表观遗传调控尚处于起步阶段,但该研究有很大潜力(借助新技术和高通量方法)快速提供新的生物标志物(诊断和/或预后),帮助肿瘤识别/分类,并为临床医生和病理学家提供新的治疗靶点。

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