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

RIZ1 negatively regulates ubiquitin-conjugating enzyme E2C/UbcH10 via targeting c-Myc in meningioma.
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RIZ1 通过靶向脑膜瘤中的 c-Myc 负向调节泛素结合酶 E2C/UbcH10。

DOI:
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发表时间:
2017-05
影响因子:
2.2
通讯作者:
胡国汉
胡国汉
中科院分区:
医学4区
文献类型:
--
作者:
蔡铮;邹勇象;胡宏康;卢成寅;孙伟;蒋磊;胡国汉

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RIZ1被认为是一个重要的肿瘤抑制基因。我们以前的研究已经证明,RIZ1的表达与脑膜瘤的发生发展密切相关。此外,我们还发现UbcH10的表达与脑膜瘤的病理分级有关,这也影响了这些患者的预后。然而,我们对UbcH10在脑膜瘤细胞中对细胞增殖、细胞凋亡、细胞周期等功能的影响还缺乏了解。此外,RIZ1和UbcH10之间的调控机制还不清楚。在本研究中,我们试图证明UbcH10是RIZ1的下游靶点,并报道了UbcH10沉默可能负向调节细胞的增殖、迁移、侵袭和促进细胞凋亡,这与过表达RIZ1的细胞表型相似。我们从机制上证明了UbcH10是c-Myc靶基因,并且RIZ1以c-Myc依赖的方式调节UbcH10的表达。本研究首次证实UbcH10在原代培养的人恶性脑膜瘤细胞的增殖、转移和凋亡中起关键作用。此外,RIZ1对UbcH10的调控机制也很清楚。我们的研究也为临床恶性脑膜瘤的后续分子干预提供了潜在的靶点和新的思路。
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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