神经母细胞瘤相关超级增强子SOX11参与形成转录核心调控网络的致病作用及机制研究

神经母细胞瘤（NB）是儿童“癌症之王”，超级增强子调控的癌基因是推动NB发生、发展的关键因素之一。SOX11是我们使用临床样本筛选，发现NB相关的重要超级增强子调控基因。进一步研究发现SOX11异常高表达与NB患儿预后不良密切相关；干扰SOX11表达，明显抑制NB细胞生长和裸鼠体内成瘤能力；结合SOX11 ChIP-seq 数据以及生物信息学分析发现SOX11可能与多个NB相关核心转录因子形成转录核心调控网络。以此为切入点，本项目拟进一步明确超级增强子SOX11在NB中发挥的具体功能，系统研究SOX11如何参与形成转录核心调控网络，揭示SOX11参与形成转录核心调控网络在NB中的致病作用和分子机制，在儿童NB临床样品中进一步解析超级增强子SOX11及其转录核心调控网络的临床意义。本项目将揭示超级增强子SOX11在NB中的功能机制，有望为儿童NB的防治提供新的理论依据和潜在的干预靶标。

Neuroblastoma（NB）is one of the most malignant tumors in children. Activation of super-enhancer regulated genes is critical for the progress of NB. We firstly use large sample screening to find that SOX11 gene is one of the most important superenhancer genes associated with NB. Further study showed that the abnormal high expression of SOX11 was closely related to the poor prognosis of NB patients. Down regulation of SOX11 inhibited the growth and tumorigenesis of NB cells in vitro and in vivo. With SOX11 ChIP-seq data and bioinformatics analysis, we found that SOX11 may form core transcription regulatory circuitry (CRC) with several NB related important transcription factors. On the basis of previous research, we are going to confirm role of superenhancer related gene SOX11 in NB, focus on studying the role of SOX11 in the CRC, reveal the molecular mechanism of CRC in NB, clarify the clinical significance of SOX11and CRC in children NB clinical samples. Super Enhancer regulated gene SOX11 plays important role in NB,this project will provide new theoretical basis and potential therapeutic targets for the prevention and treatment of pediatric NB.