Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States.
Cancer Lett. 2013 Jan 1;328(1):10-7. doi: 10.1016/j.canlet.2012.08.028. Epub 2012 Aug 29.
DNA methylation is a major contributor to epigenetic alterations and as such is a potential biomarker and therapeutic target in gastrointestinal malignancies. DNA methylation is commonly observed in several Gastrointestinal (GI) malignancies including pancreatic and colorectal cancer. Methylation results in decreased expression of tumor suppressor genes. Secreted protein acidic and rich in cysteine (SPARC) is a tumor suppressor gene that can be functionally inactivated through methylation. SPARC is commonly dysregulated in GI malignancies. Inhibition of DNA methylation can reverse the silencing of SPARC. In the present review, we will discuss recent advances in our understanding of the features of DNA methylation that pertain to SPARC, focusing on their functional and clinical relevance in GI carcinogenesis.
DNA 甲基化是表观遗传改变的主要贡献者，因此是胃肠道恶性肿瘤的潜在生物标志物和治疗靶点。几种胃肠道（GI）恶性肿瘤中常见 DNA 甲基化，包括胰腺癌和结直肠癌。甲基化导致肿瘤抑制基因表达减少。富含半胱氨酸的酸性分泌蛋白（SPARC）是一种肿瘤抑制基因，可通过甲基化使其功能失活。SPARC 在 GI 恶性肿瘤中通常失调。抑制 DNA 甲基化可以逆转 SPARC 的沉默。在本综述中，我们将讨论我们对与 SPARC 相关的 DNA 甲基化特征的最新认识方面的进展，重点讨论它们在 GI 癌变中的功能和临床相关性。
