视网膜母细胞瘤（RB）属罕见恶性肿瘤，其恶性程度高，可致盲、致残、致死，是儿童最常见的眼内恶性肿瘤，严重危害患儿的生命和生活质量。研究发现抑癌基因RB1突变可导致RB发生，近期有报道RB1基因正常也可发生RB，其发生机制不明。我们发现，在无RB1突变的RB细胞中存在染色体13q14基因组区异常构象，通过crispr/cas9技术破坏该异常构象，能显著抑制RB细胞的体内外增殖能力，且构象相关蛋白CCCTC结合因子（CTCF）在RB1启动子区和新发现构象区均有较强的结合。据此推测：CTCF可能通过介导RB1启动子与抑制子之间形成异常三维构象，导致抑癌基因RB1失活，进而促进RB发生。因此，本项目拟以染色体构象重塑为突破口，利用染色体构象捕获、DNA亲和吸附洗脱等技术，探究关键构象形成因子CTCF在RB1转录调控中的作用，了解RB发生的染色体构象重塑机制，为探寻RB潜在治疗靶点提供新依据。

Retinoblastoma (RB) is a rare malignant tumor, but it is the most common intraocular tumor in children. It is a major disease that causes blindness, disability, death and serious harm to the quality of life. Early studies suggested that the mutation of tumor suppressor gene RB1 was the main inducement of RB tumorigenesis. However, many RB patients were found not to be related to RB1 mutation, and the mechanism was still unknown. Previous research found that an chromosome 13q14 abnormal conformation existed in the RB cells without RB1 mutation. Destroying the abnormal conformation through crispr/cas9 could inhibit the proliferation of RB cells in vivo and vitro. And there is a strong combination between conformation-related protein CCCTC binding factor (CTCF) and RB1 promoter region and the newly found conformation area. Accordingly, We suggest that CTCF may promote retinoblastoma tumorigenesis by causing abnormal conformation in chromosome 13q14. In this project, we use methods such as chromosome conformation capture (3C) and DNA affinity adsorption to further explore the role of key conformational formation factor CTCF in RB1 transcription regulation. Therefore to clarify the chromosome conformation remodeling mechanism in RB tumorigenesis. We look forward to provide a potential therapeutic targets for RB and rich the chromosome conformation theory of tumorigenesis.