小脑髓母细胞瘤(MB)是发生在儿童和婴幼儿小脑中的恶性肿瘤。异常的神经元分化可能导致脑肿瘤，拓扑异构酶IIβ(Top IIβ)在神经元分化中发挥重要作用。本研究旨在研究13-顺-视黄醇酸(13-cis RA)促进在人类MB Daoy细胞中表达Top IIβ和诱导神经元分化的分子机制。结果显示，13-cis RA抑制了细胞增殖，诱导了细胞周期在G0/G1期间停滞。细胞分化成神经表型，表达神经标记微管相关蛋白2(MAP2)和丰富的Top IIβ，显著的神经突起生长。染色质免疫沉淀(ChIP)试验显示，13-cis RA诱导细胞分化后，Top IIβ启动子中组蛋白H3的赖氨酸27三甲基化(H3K27me3)修饰降低，而蕈菌酸结构域含蛋白3(JMJD3)在Top IIβ启动子中的结合增加。这些结果表明，H3K27me3和JMJD3可以调节Top IIβ基因的表达，与诱导神经分化有关。我们的结果提供了对Top IIβ在神经分化过程中调控机制的新见解，并暗示了13-cis RA在MB的临床治疗中的潜在应用。© 2023作者，根据Springer Science+Business Media、LLC和Springer Nature的独家许可。

Medulloblastoma (MB) is a malignant tumor of the cerebellum that occurs in children and infants. Abnormal neuronal differentiation can lead to brain tumors, and topoisomerase IIβ (Top IIβ) plays an important role in neuronal differentiation. The aim of this study was to investigate the molecular mechanism of 13-cis retinoic acid (13-cis RA) promoting the expression of Top IIβ and inducing neuronal differentiation in human MB Daoy cells. The results showed that 13-cis RA inhibited the cell proliferation and induced cell cycle arrest in G0/G1 phase. The cells differentiated into a neuronal phenotype, with high expression of the neuronal marker microtubule-associated protein 2 (MAP2) and abundant Top IIβ, and obvious neurite growth. Chromatin immunoprecipitation (ChIP) assay showed that histone H3 lysine 27 tri-methylation (H3K27me3) modification in Top IIβ promoter decreased after 13-cis RA-induced cell differentiation, while jumonji domain-containing protein 3 (JMJD3) binding in Top IIβ promoter increased. These results suggest that H3K27me3 and JMJD3 can regulate the expression of Top IIβ gene, which is related to inducing neural differentiation. Our results provide new insights into understanding the regulatory mechanisms of Top IIβ during neuronal differentiation and imply the potential application of 13-cis RA in the clinical treatment of MB.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.