神经母细胞瘤（NB）是最常见的儿童交感神经系统颅外恶性肿瘤。顺铂和阿霉素可造成DNA双链断裂导致细胞死亡，是NB治疗常用化疗药物。研究NB细胞DNA损伤修复机制对于提高化疗疗效具有重要的科学价值和临床意义。本课题组发现，转录调节因子KAISO在高危型NB中高表达；在SH-SY5Y细胞中，KAISO与DNA双链断裂修复标记分子γH2AX在DNA损伤位点共定位；此外，降低KAISO表达，可抑制SH-SY5Y细胞增殖，增加NB细胞对顺铂和阿霉素的敏感性。据此提出科学假设：KAISO除了作为转录调节因子发挥作用外，还可能作为一个新的信号分子直接参与DNA双链断裂修复的信号转导，进而促进NB发生发展，降低NB化疗敏感性。本研究旨在揭示KAISO参与DNA双链断裂修复的新功能及其调控机制，并通过临床数据明确KAISO高表达可促进NB发生发展并产生化疗耐药，为NB临床诊疗提供线索和理论依据。

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood that arises from the developing sympathetic nervous system. Cisplatin (CDDP) and Adriamycin (ADR) are frequently-used chemotherapy drugs, which leading to tumor cells death by inducing DNA double strand breaks (DSBs). It is important to study the mechanisms of DNA damage and repair in NB cells, which can improve the prognosis of children patients with NB. Based on literature investigation and experiments, significant higher expression of transcriptional regulator KAISO is found in the high-risk group of NB. Meanwhile, high expression level of KAISO promotes the proliferation of NB cell line SH-SY5Y and decreases the sensitivity of SH-SY5Y to chemotherapeutic agent CDDP and ADR. In addition, KAISO exhibits the selective accumulation at laser tracts, colocalizing with γH2AX, a distinctive marker of DSBs. It implied that KAISO has new functions in DNA double strand break repair (DSBR). We provide our scientific hypothesis: as a signal molecule, KAISO promotes the development, progression and chemotherapy resistance of NB through advancing the ability of DSBR in NB cells. This study is aim to reveal that the new roles of KAISO in DSBR; exploring the molecular mechanisms of KAISO involved in DSBR; explicating that high expression of KAISO boosts the development, progression and chemotherapy resistance of NB by clinical NB samples. In summary, this project will provide evidences that KAISO is a novel biomarker for prognosis of NB and reveal the molecular mechanisms of chemotherapy resistance in NB.