增殖失控是恶性脑膜瘤发生发展过程中的重要机制，前期研究发现RIZ1表达与脑膜瘤级别呈负相关，在恶性脑膜瘤细胞中过表达RIZ1可抑制细胞增殖并导致G2/M期阻滞，但其分子机制尚不明确。后进一步发现RIZ1与c-Myc、UbcH10呈关联表达，过表达RIZ1可下调c-Myc、UbcH10表达，并激活导致G2/M期阻滞。因此，我们推测RIZ1可能通过UbcH10等表达调控脑膜瘤恶性增殖。本课题拟应用RNA干扰、过表达等方法，研究RIZ1通过c-Myc、UbcH10调控脑膜瘤细胞增殖的分子机制；然后通过荧光素酶活性检测联合ChIP实验，探讨RIZ1对UbcH10的转录调控作用；最后通过体内试验和临床标本分析验证RIZ1对c-Myc、UbcH10的调控及其与脑膜瘤恶性增殖的关联。研究结果有望阐明RIZ1通过UbcH10调控脑膜瘤增殖的机制，并可能为恶性脑膜瘤增殖失控的分子干预提供潜在靶点。

Proliferation dysregulation plays a critical role in the development and progression of malignant meningioma. Our previous study demonstrated that expression levels of RIZ1 were inversely associated with pathological grade of meningioma and forced expression of RIZ1 might inhibit proliferation of meningioma cells via G2/M arrest. However, the intrinsic molecular regulatory mechanism remains largely unclear. Moreover, we found thatforced expression of RIZ1 may downregulate expression levels of c-Myc and UbcH10 and thus activate G2/M checkpoint. Therefore, we speculate that RIZ1 may compromise the mitotic checkpoint function and promote cell proliferation via inducing UbcH10 expression in meningioma cells. In this study, firstly, the mechanisms of cell proliferation mediated by RIZ1 via inducing UbcH10 expression were investigated by using RNA interference and overexpression assay. Secondly, the regulatory mechanisms of UbcH10 biosynthesis mediated by RIZ1 were investigated by using luciferase reporter assay and ChIP assay. Finally, in vivo study and retrospective clinical study were employed to verify the regulatory mechanisms of RIZ1 on UbcH10 biosynthesis and the association with cell proliferaion. These results may demonstrate the mechanisms of cell proliferation mediated by RIZ1 via inducing UbcH10 expression and may offer potential therapeutic targets for the molecular intervention of malignant proliferation.