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膀胱癌中的表观遗传学

Epigenetics in bladder cancer.

作者信息

Enokida Hideki, Nakagawa Masayuki

机构信息

Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.

出版信息

Int J Clin Oncol. 2008 Aug;13(4):298-307. doi: 10.1007/s10147-008-0811-1. Epub 2008 Aug 15.

Abstract

Bladder cancer (BC) is the second most common malignancy of the genitourinary tract and the second leading cause of cancer death in patients with urinary tract malignancies. DNA methylation and histone modifications are important epigenetic mechanisms of gene regulation and play essential roles both independently and cooperatively in tumor initiation and progression. Aberrant epigenetic events such as DNA hypermethylation and altered histone acetylation have both been observed in bladder cancer, in which they affect a large number of genes. Although the list of aberrantly epigenetically regulated genes continues to grow, combination analysis including several candidate genes has given promising results of potential tumor biomarkers for the early diagnosis and risk assessment of bladder cancer. Thus, large-scale screening of aberrant epigenetic events such as DNA hypermethylation is needed to identify bladder cancer-specific epigenetic fingerprints. The reversibility of epigenetic aberrations has made them attractive targets for cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases, leading to the reactivation of silenced genes. In this review, we examine the current literature on epigenetic changes in bladder cancer and discuss the clinical potential of cancer epigenetics for the diagnosis and treatment of this disease.

摘要

膀胱癌(BC)是泌尿生殖道第二常见的恶性肿瘤,也是尿路恶性肿瘤患者癌症死亡的第二大主要原因。DNA甲基化和组蛋白修饰是基因调控的重要表观遗传机制,在肿瘤的发生和发展过程中,它们各自独立发挥作用,同时也相互协作,发挥着至关重要的作用。在膀胱癌中,已观察到诸如DNA高甲基化和组蛋白乙酰化改变等异常表观遗传事件,这些事件会影响大量基因。尽管异常表观遗传调控基因的清单在不断增加,但对包括多个候选基因在内的联合分析,已为膀胱癌早期诊断和风险评估的潜在肿瘤生物标志物带来了有前景的结果。因此,需要对DNA高甲基化等异常表观遗传事件进行大规模筛查,以识别膀胱癌特异性表观遗传指纹。表观遗传畸变的可逆性使其成为使用使DNA去甲基化和抑制组蛋白脱乙酰酶的调节剂进行癌症治疗的有吸引力的靶点,从而导致沉默基因的重新激活。在这篇综述中,我们研究了关于膀胱癌表观遗传变化的当前文献,并讨论了癌症表观遗传学在该疾病诊断和治疗中的临床潜力。

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