基于SELEX方法研究增强子差异甲基化影响前列腺癌风险的分子机制

前列腺癌作为一种常见的恶性肿瘤，严重威胁着男性的健康，它的发生、发展跟转录调控密切相关。但与转录调控活性紧密相关的增强子差异甲基化在前列腺癌发生、发展中的调控机理仍不清楚。本研究将利用甲基化敏感SELEX（systematic evolution of ligands by exponential enrichment）方法系统对比研究16个前列腺癌相关转录因子在增强子发生差异甲基化时结合特异性的改变；然后，利用ENCODE数据库中前列腺癌细胞系LNCaP的Hi-C数据预测与转录因子相互作用的增强子调控的靶基因，并在前列腺癌细胞系LNCaP中进行功能验证，从而解析关键增强子差异甲基化在前列腺癌发生、发展中的调控机理。本研究不仅为阐明前列腺癌发生、发展的机制提供了新思路，更为今后临床上寻找治疗前列腺癌的新药物提供了更多靶位点。

Prostate cancer, a common malignancy in men, poses a serious threat to human health, whose occurrence and development are closely related to transcriptional regulation. Cytosine methylation occurring at enhancer is tightly associated with the transcriptional regulatory activity. However, it remains unclear how differential methylation of enhancer affects the initiation and progression of prostate cancer. In this study, we set out to study the differential binding affinity of 16 transcription factors (TFs) that are known to play a significant regulatory role in tumorigenesis of prostate cancer by employing the methylation-sensitive systematic evolution of ligands by an exponential enrichment (SELEX) method, which can help us find that how TF binding will be affected by differential methylation of enhancers. Integration of Hi-C data conducted in prostate cancer cell LNCaP to predict target genes regulated by these enhancers, in concert with functional verification will pave a way to reveal the regulatory mechanism of the methylation at key enhancers in the initiation and progression of prostate cancer. Taken together, this study not only provides a new idea for elucidating the initiation and progression of prostate cancer, but also offers potential targets for new drugs to treat prostate cancer.