The circular RNA circ-Ccnb1 dissociates Ccnb1/Cdk1 complex suppressing cell invasion and tumorigenesis
The circular RNA circ-Ccnb1 dissociates Ccnb1/Cdk1 complex suppressing cell invasion and tumorigenesis
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环状 RNA circ-Ccnb1 解离 Ccnb1/Cdk1 复合物，抑制细胞侵袭和肿瘤发生
DOI：
10.1016/j.canlet.2019.05.036
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Yang, Burton B.
中科院分区：
文献类型：
--
作者：
Fang, Ling;Du, William W.;Yang, Burton B.
环状RNA是一大类在哺乳动物中广泛表达的非编码RNA。然而，环状RNA的功能在很大程度上是未知的。我们最近报道，在突变型P53细胞中，环状RNA CIRC-Ccnb1可以与H_2AX结合，并抑制突变型P53在肿瘤进展中的作用。我们发现CIRC-Ccnb1可以与Ccnb1和CDK1蛋白相互作用。正常情况下，Ccnb1和CDK1蛋白形成复合体，允许Ccnb1作为细胞有丝分裂的全有或全无开关发挥作用。CIRC-Ccnb1与Ccnb1和CDK1蛋白的相互作用解离了Ccnb1-CDk1复合体的形成，形成了一个包含CIRC-Ccnb1、Ccnb1和CDk1的大复合体。这种大型复合体的形成可能发生在胞浆和细胞核中，Ccnb1失去了促进细胞迁移、侵袭、增殖和存活的作用。在体内，异位传递CIRC-Ccnb1抑制了肿瘤的生长并延长了小鼠的存活时间。这些结果为CIRC-Ccnb1在体外和体内调节肿瘤进展增加了另一层机制。
Circular RNAs represent a large class of non-coding RNAs that are extensively expressed in mammals. However, the functions of circular RNAs are largely unknown. We recently reported that the circular RNA circ-Ccnb1 could bind with H2AX in p53 mutant cells and suppressed mutant p53 in tumor progression. Here we found that circ-Ccnb1 could interact with both Ccnb1 and Cdk1 proteins. Normally, Ccnb1 and Cdk1 proteins form a complex, allowing Ccnb1 to function as an all-or-none switch for cell mitosis. The interaction of circ-Ccnb1 with Ccnb1 and Cdk1 proteins dissociated the formation of Ccnb1-Cdk1 complex, by forming a large complex containing circ-Ccnb1, Ccnb1 and Cdk1. Formation of this large complex may occur in cytosol and nuclei, and Ccnb1 loses its roles in enhancing cell migration, invasion, proliferation and survival. In vivo, ectopic delivery of circ-Ccnb1 inhibited tumor growth and extended mouse viability. These results have added another layer of mechanisms for circ-Ccnb1 to regulate tumor progression in vitro and in vivo.