RIZ1 negatively regulates ubiquitin-conjugating enzyme E2C/UbcH10 via targeting c-Myc in meningioma

RIZ1 通过靶向脑膜瘤中的 c-Myc 负向调节泛素结合酶 E2C/UbcH10

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作者:Zheng Cai, Yongxiang Zou, Hongkang Hu, Chengyin Lu, Wei Sun, Lei Jiang, Guohan Hu

Abstract

RIZ1 has been considered as an important tumor suppressor gene. Our previous studies have already demonstrated that the expression of RIZ1 is closely related to the occurrence and development of meningioma. In addition, we also found that the expression of UbcH10 was related to the pathologic grade of meningioma which also affected the prognosis of these patients. However, we are lack of the understanding of the effect of UbcH10 on cell proliferation, cell apoptosis, cell cycle and other functions in meningioma cells. Besides, the regulation mechanism between RIZ1 and UbcH10 still remains unclear. In this study, we attempted to demonstrated that UbcH10 was a downstream target of RIZ1 and reported that UbcH10 silencing might negatively regulate cell proliferation, migration, invasion and promote apoptosis, which is similar to the cell phenotype that of over expressed RIZ1. Mechanistically, we proved that UbcH10 was a c-Myc target gene and that RIZ1 regulated UbcH10 expression in a c-Myc-dependent manner. For the first time, our study demonstrated that UbcH10 played a key role in the proliferation, metastasis and apoptosis of primary human malignant meningioma cells. In addition, the mechanism of RIZ1 regulating UbcH10 is also clear. Our study can also provide a potential target and new idea for the follow-up molecular intervention in clinical malignant meningiomas.

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