神经母细胞瘤患儿预后不良的主要原因是肿瘤的远处转移，HNF4A是调控神经母细胞瘤侵袭转移的关键靶标，但其活化调控机制不明。前期研究发现在神经母细胞瘤中CBP可通过乙酰化修饰维持HNF4A核定位及与染色质的结合状态；而HNF4A-AS1-SEP2可通过结合ASF1蛋白，干扰ASF1与CBP的相互作用，抑制CBP对HNF4A的乙酰化修饰，从而抑制肿瘤侵袭转移。因此，我们提出“HNF4A-AS1-SEP2通过结合ASF1蛋白，干扰ASF1与CBP的相互作用，抑制CBP对HNF4A的乙酰化修饰，从而抑制神经母细胞瘤侵袭转移”的假说。拟运用二维电泳质谱检测、蛋白质免疫共沉淀、免疫荧光、FRET等分子生物学技术，结合细胞及动物学实验方法，进一步研究HNF4A-AS1-SEP2对HNF4A的调节作用，并对其机制进行深入研究，为临床诊治神经母细胞瘤提供新的思路。

The main poor prognosis cause for neuroblastoma is tumor distant metastasis. HNF4A is a crucial factor in regulating the invasion and metastasis of neuroblastoma, however its activation regulation mechanisms remain unclear. Our preliminary experiments found, in neuroblastoma, CBP maintains HNF4A nuclear localization and binding to chromatin through acetylation modification. Moreover, our results indicated that HNF4A-AS1-SEP2 bond with ASF1, interfered ASF1 interaction with CBP, and suppressed the acetylation modification of HNF4A by CBP, thereby reducing the invasiveness and metastasis of neuroblastoma. Therefore, we proposed a scientific hypothesis: HNF4A-AS1-SEP2 inhibits the acetylation modification of HNF4A via interfering ASF1 interaction with CBP, thus inhibits neuroblastoma invasion and metastasis. To validate this hypothesis and further explore its underlying mechanisms, we intend to apply a series of techniques including molecular, cellular biology, and animal xenograft tumor models. The results of this study will provide new choices for clinical diagnosis and treatment of neuroblastoma.