Hong Jang Hee, Jin Eun-Heui, Kim Soyeon, Song Kyu-Sang, Sung Jae Kyu
Clinical Trials Center, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea.
Department of Pharmacology, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea.
Oncol Lett. 2018 May;15(5):6666-6670. doi: 10.3892/ol.2018.8121. Epub 2018 Feb 27.
DNA methylation is an important epigenetic modification that alters gene expression; DNA hypomethylation contributes to tumorigenesis through multiple processes. In the present study, the methylation of long interspersed element-1 (LINE-1) in 95 gastric cancer (GC) tissues and matched adjacent normal tissues was investigated by pyrosequencing. LINE-1 methylation was compared with the expression of ubiquitin-like with PHD and ring-finger protein 1 (UHRF1), an essential regulator of DNA methylation, using reverse transcription-quantitative polymerase chain reaction. Significant hypomethylation of LINE-1 and overexpression of UHRF1 were observed in GC tissues compared with the matched controls (P<0.001 and P=0.001, respectively). LINE-1 hypomethylation was inversely correlated with UHRF1 overexpression in GC tissues (r=-0.026, P=0.028). In addition, LINE-1 hypomethylation in GC was significantly associated with Lauren's histological classification, tumor differentiation and background intestinal metaplasia (P=0.014, P=0.042 and P=0.034, respectively). These results suggest that LINE-1 hypomethylation may be a potential biomarker for GC and it is indirectly regulated by UHRF1 overexpression.
DNA甲基化是一种重要的表观遗传修饰，可改变基因表达；DNA低甲基化通过多种过程促进肿瘤发生。在本研究中，采用焦磷酸测序法检测了95例胃癌（GC）组织及配对的癌旁正常组织中长散在核元件1（LINE-1）的甲基化情况。使用逆转录定量聚合酶链反应将LINE-1甲基化与DNA甲基化的关键调节因子泛素样含PHD和环指蛋白1（UHRF1）的表达进行比较。与配对的对照相比，GC组织中观察到LINE-1显著低甲基化和UHRF1过表达（分别为P<0.001和P=0.001）。GC组织中LINE-1低甲基化与UHRF1过表达呈负相关（r=-0.026，P=0.028）。此外，GC中LINE-1低甲基化与劳伦组织学分类、肿瘤分化和背景肠化生显著相关（分别为P=0.014、P=0.042和P=0.034）。这些结果表明，LINE-1低甲基化可能是GC的潜在生物标志物，并且它受UHRF1过表达的间接调节。
