ANKRD18A as a novel epigenetic regulation gene in lung cancer
ANKRD18A as a novel epigenetic regulation gene in lung cancer
复制标题
ANKRD18A作为肺癌的新型表观遗传调控基因
DOI：
10.1016/j.bbrc.2012.10.116
复制
发表时间：
2012-12-14
影响因子：
3.1
通讯作者：
Liu, Jin-yi
中科院分区：
文献类型：
--
作者：
Liu, Wen-bin;Han, Fei;Liu, Jin-yi
肺癌是世界范围内癌症相关死亡的最常见原因之一。有效的肺癌早期诊断和靶向治疗以降低发病率和死亡率将受益于更好地了解肺癌发生和发展过程中从正常到恶性肿瘤细胞发生的关键分子变化，但这些变化在很大程度上是未知的。以往的研究表明，DNA甲基化是基因表达调控的重要机制，在肺癌发生中起着关键作用。在本研究中，我们筛选了一个新的甲基化基因。ANKRD 18 A，编码锚蛋白重复结构域18 A，以确定其是否受肺癌中DNA甲基化的调控。采用甲基化特异性PCR和亚硫酸氢盐测序PCR分析基因甲基化状态，实时定量逆转录聚合酶链反应（qRT-PCR）检测mRNA水平。肺癌组织中ANKRD 18 A基因启动子甲基化率为68.4%（26/38），而正常肺组织中ANKRD 18 A基因启动子甲基化率为0/20（P < 0.01），肺癌组织中ANKRD 18 A mRNA表达水平明显低于癌旁正常肺组织。此外，我们发现ANKRD 18 A表达在10个肺癌细胞系中的9个中显著降低。这与ANKRD 18 A启动子区域的高甲基化有关。此外，ANKRD 18 A在甲基化肺癌细胞系中的弱表达在用DNA甲基化抑制剂5-氮杂-2 '-脱氧胞苷处理后显著增加。这些结果表明，ANKRD 18 A高甲基化和随之而来的mRNA改变可能是肺癌的重要分子机制。(C)2012 Elsevier Inc. All rights reserved.
Lung cancer is one of the most common causes of cancer-related mortality worldwide. Effective early diagnosis and targeted therapies for lung cancer to reduce incidence and mortality would benefit from a better understanding of the key molecular changes that occur from normal to malignant tumor cells during lung cancer initiation and development, but these are largely unknown. Previous studies have shown that DNA methylation, an important mechanism for the regulation of gene expression, plays a key role in lung carcinogenesis. In this study, we screened a novel methylation gene. ANKRD18A, encoding ankyrin repeat domain 18A, to determine whether it is regulated by DNA methylation in lung cancer. Methylation-specific PCR and bisulfite sequencing PCR were used to analyze gene methylation status, and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) examined mRNA levels. Promoter hypermethylation of ANKRD18A was detected in 68.4% (26/38) of lung cancer tissues but not (0/20) in normal lung tissues (P < 0.01), whereas ANKRD18A mRNA expression was significantly decreased in lung cancer tissues compared with adjacent normal tissues. In addition, we found that ANKRD18A expression was significantly decreased in 9, of 10 lung cancer cell lines. This was associated with hypermethylation of the ANKRD18A promoter region. Moreover, weak expression of ANKRD18A in methylated lung cancer cell lines increased markedly after treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine. These results suggest that ANKRD18A hypermethylation and consequent mRNA alterations might be a vital molecular mechanism in lung cancer. (C) 2012 Elsevier Inc. All rights reserved.