Dasan Undergraduate College, Ajou University, Suwon 16499, Korea.
Graduate School of New Drug Discovery & Development, Chungnam National University, Daejeon 34134, Korea.
Viruses. 2020 May 20;12(5):565. doi: 10.3390/v12050565.
Selenium binding protein 1 (SELENBP1) has been known to be reduced in various types cancer, and epigenetic change is shown to be likely to account for the reduction of expression. With cDNA microarray comparative analysis, we found that SELENBP1 is markedly decreased in hepatitis B virus-X (HBx)-expressing cells. To clarify the effect of HBx on expression, we compared the expression levels of mRNA and protein by semi-quantitative RT-PCR, Northern blot, and Western blot. As expected, expression was shown to be reduced in cells expressing HBx, and reporter gene analysis showed that the promoter is repressed by HBx. In addition, the stepwise deletion of 5' flanking promoter sequences resulted in a gradual decrease in basal promoter activity and inhibition of expression by HBx. Moreover, immunohistochemistry on tissue microarrays containing 60 pairs of human liver tissue showed decreased intensity of SELENBP1 in tumor tissues as compared with their matched non-tumor liver tissues. Taken together, our findings suggest that inhibition of expression by HBx might act as one of the causes in the development of hepatocellular carcinoma caused by HBV infection.
硒结合蛋白 1（SELENBP1）已被证实存在于多种类型的癌症中表达降低，表观遗传改变可能是其表达降低的原因。通过 cDNA 微阵列比较分析，我们发现乙型肝炎病毒 X（HBx）表达细胞中 SELENBP1 明显减少。为了阐明 HBx 对 表达的影响，我们通过半定量 RT-PCR、Northern blot 和 Western blot 比较了 HBx 表达细胞中 mRNA 和蛋白的表达水平。正如预期的那样，HBx 表达细胞中 表达降低，报告基因分析表明 HBx 抑制 启动子。此外，5' 侧翼启动子序列的逐步缺失导致基础启动子活性逐渐降低，HBx 抑制 表达。此外，含有 60 对人肝组织的组织微阵列的免疫组织化学分析显示，与匹配的非肿瘤肝组织相比，肿瘤组织中 SELENBP1 的强度降低。总之，我们的研究结果表明，HBx 抑制 表达可能是乙型肝炎病毒感染导致肝细胞癌发生的原因之一。
