Kwon Mi Jeong, Shin Young Kee
Advanced Institutes of Convergence Technology, Suwon, Kyeonggi-do 443-270, Korea; E-Mail:
Int J Mol Sci. 2011 Jan 31;12(2):983-1008. doi: 10.3390/ijms12020983.
The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except for the DNA hypomethylation of some genes. Recently, we reported that the overexpression of cancer-promoting genes in ovarian cancer is associated with the loss of repressive histone modifications. This discovery suggested that epigenetic derepression may contribute to ovarian tumorigenesis by constituting a possible mechanism for the overexpression of oncogenes or cancer-promoting genes in tumors. The emerging importance of epigenetic aberrations in tumor initiation and in the regulation of cancer-initiating cells, suggests that epigenetically regulated genes may be promising therapeutic targets and biomarkers. Given that the current challenges in ovarian cancer include the identification of biomarkers for early cancer detection and the discovery of novel therapeutic targets for patients with recurrent malignancies undergoing chemotherapy, understanding the epigenetic changes that occur in ovarian cancer is crucial. This review looks at epigenetic mechanisms involved in the regulation of cancer-associated genes, including the contribution of epigenetic derepression to the activation of cancer-associated genes in ovarian cancer. In addition, possible epigenetic therapies targeting epigenetically dysregulated genes are discussed. A better understanding of the epigenetic changes in ovarian cancer will contribute to the improvement of patient outcomes.
表观遗传异常在肿瘤发生和发展中的作用现已得到充分证实。然而，大多数研究集中在肿瘤发生过程中肿瘤抑制基因的表观遗传失活，除了一些基因的DNA低甲基化外，对于癌症相关基因的表观遗传激活知之甚少。最近，我们报道卵巢癌中促癌基因的过表达与抑制性组蛋白修饰的缺失有关。这一发现表明，表观遗传去抑制可能通过构成肿瘤中癌基因或促癌基因过表达的一种可能机制，从而促进卵巢肿瘤的发生。表观遗传异常在肿瘤起始和癌症起始细胞调控中的重要性日益凸显，这表明表观遗传调控的基因可能是有前景的治疗靶点和生物标志物。鉴于卵巢癌目前面临的挑战包括识别早期癌症检测的生物标志物以及为接受化疗的复发性恶性肿瘤患者发现新的治疗靶点，了解卵巢癌中发生的表观遗传变化至关重要。本综述探讨了参与癌症相关基因调控的表观遗传机制，包括表观遗传去抑制对卵巢癌中癌症相关基因激活的作用。此外，还讨论了针对表观遗传失调基因的可能表观遗传疗法。更好地了解卵巢癌中的表观遗传变化将有助于改善患者预后。
