Long noncoding RNA UCA1 promotes tumour metastasis by inducing GRK2 degradation in gastric cancer
Long noncoding RNA UCA1 promotes tumour metastasis by inducing GRK2 degradation in gastric cancer
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长非编码RNA UCA1通过诱导胃癌GRK2降解促进肿瘤转移
DOI：
10.1016/j.canlet.2017.08.013
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发表时间：
2017-11-01
期刊：
影响因子：
9.7
通讯作者：
Zhu, Zhenggang
中科院分区：
文献类型：
--
作者：
Wang, Zhen-qiang;He, Chang-yu;Zhu, Zhenggang
越来越多的证据表明，长链非编码RNA（lncRNA）通过影响转录和转录后过程来调节基因和蛋白质的表达。在这里，我们报告说，lncRNA UCA 1增加胃癌（GC）细胞的转移能力，通过调节GRK 2蛋白的稳定性，促进Cbl-c介导的GRK 2泛素化和降解。这个过程激活了ERK-MMP 9信号通路。此外，我们证明GRK 2在GC细胞中下调，GRK 2的沉默可能会导致类似的表型变化和信号通路激活，如在GC细胞中UCA 1升高所诱导的那些。我们的研究结果表明，UCA 1可能作为蛋白质泛素化的介导剂，并可能是一个有前途的分子靶点GC治疗。(C)2017爱思唯尔B. V.保留所有权利。
Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) regulate gene and protein expression by exerting an influence on transcriptional and post-transcriptional processes. Here, we report that the lncRNA UCA1 increases the metastatic ability of gastric cancer (GC) cells by regulating GRK2 protein stability by promoting Cbl-c-mediated GRK2 ubiquitination and degradation. This process then activates the ERK-MMP9 signalling pathway. Furthermore, we demonstrate that GRK2 is downregulated in GC cells and that silencing of GRK2 might cause similar phenotypic changes and signalling pathway activation as those induced by elevated UCA1 in GC cells. Our results suggest that UCA1 might function as a mediator of protein ubiquitination and may be a promising molecular target for GC therapy. (C) 2017 Elsevier B.V. All rights reserved.