Motalleb Gholamreza, Gholipour Naghmeh, Samaei Nader Mansour
Department of Biology, Faculty of Science, University of Zabol, P.O. Box 98615-53, Zabol, Iran,
Med Oncol. 2014 Apr;31(4):916. doi: 10.1007/s12032-014-0916-5. Epub 2014 Mar 22.
Central role of astrocyte elevated gene-1 (AEG-1) in regulating diverse aspects of hepatocellular carcinoma (HCC) pathogenesis and association of its overexpression with HCC progression has been demonstrated. The positive regulatory regions of AEG-1 promoter contain several putative transcription factor binding sites critical for basal promoter activity. In this study, the aim was to explore the association of AEG-1 promoter variant with HCC. In this study, the human AEG-1 promoter including the region -538 to -42 was explored in 53 HCC patients and 108 healthy controls. The polymerase chain reaction-sequencing method was used for investigating AEG-1 promoter polymorphisms. A novel mutation in AEG-1 promoter in human HCC patients at a potential AP-2 binding site was explored. An A>C mutation was observed in -483 of AEG-1 promoter in 4 out of 53 HCC patients but not in 108 control individuals. Sequencing data showed genetic variations in 11 HCC patients and 3 healthy controls. Among them, one novel SNP was found in activator protein-1 (AP2), a transcription factor binding site (-483 A to C) that may be associated with the susceptibility to HCC (P = 0.012) but no associations were found for other observed variations. This mutation could be tumor-specific. AEG-1 promoter variant -483 A>C may be associated with the susceptibility to HCC in Iranian population. To our knowledge, this is the first study that has reported this association with the susceptibility to HCC. Therefore, further studies need to be conducted in larger sample sizes and other populations to validate these findings.
星形胶质细胞上调基因-1（AEG-1）在调节肝细胞癌（HCC）发病机制的多个方面所起的核心作用及其过表达与HCC进展的关联已得到证实。AEG-1启动子的正调控区域包含几个对基础启动子活性至关重要的假定转录因子结合位点。在本研究中，目的是探讨AEG-1启动子变异与HCC的关联。在本研究中，对53例HCC患者和108例健康对照者的人AEG-1启动子（包括-538至-42区域）进行了研究。采用聚合酶链反应测序法研究AEG-1启动子多态性。探索了人类HCC患者AEG-1启动子在一个潜在AP-2结合位点的新突变。在53例HCC患者中有4例在AEG-1启动子的-483处观察到A>C突变，但在108例对照个体中未观察到。测序数据显示11例HCC患者和3例健康对照存在基因变异。其中，在转录因子结合位点激活蛋白-1（AP2）（-483 A至C）中发现一个新的单核苷酸多态性（SNP），其可能与HCC易感性相关（P = 0.012），但其他观察到的变异未发现相关性。该突变可能是肿瘤特异性的。AEG-1启动子变异-483 A>C可能与伊朗人群的HCC易感性相关。据我们所知，这是首次报道这种与HCC易感性的关联。因此，需要在更大样本量和其他人群中进行进一步研究以验证这些发现。
