Investigation of Imprinting mechanism between Beckwith-Wiedemann syndrome and Wilms tumor

Beckwith Wiedeman综合征（BWS）与Wilms肿瘤高发，11p15.5染色体上KvDMR结构域DNA去甲基化已被频繁观察到。事实上，kcnq10t1基因的绝对或相对过表达会抑制同一等位基因上的周围基因。为了抑制kcnq10t1基因的表达，设计了两种PI聚酰胺来识别启动子区域的CCAAT盒。经这些PI聚酰胺处理后，在G401（Wilms）肿瘤细胞系中观察到kcnq10t1基因的显著下调和生长抑制。结果表明，这些PI聚酰胺可能成为治疗Wilms肿瘤和其他KvDMR结构域印迹缺失肿瘤的新药物。

In Beckwith Wiedeman syndrome(BWS), which occur in conjunction with Wilms tumor at high rates, DNA demethylation of KvDMR domain on chromosome 11p15.5 has been frequently observed. In fact, absolute or relative overexpression of KCNQ1OT1 gene inhibits circumjacent genes on same allele. To suppress KCNQ1OT1 gene expression, two PI polyamides were designed to recognize CCAAT box of promoter region. After the treatment with those PI polyamides, significant down-regulation of KCNQ1OT1 gene and growth inhibition were observed in G401(Wilms tumor cell lines). The results indicate that these PI polyamides could be new therapeutic agents for Wilms tumor and other tumors which has Loss of Imprinting in KvDMR domain.