Journal
CANCER LETTERS
Volume 408, Issue -, Pages 10-21Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.08.013
Keywords
lncRNA; UCA1; Gastric cancer; Ubiquitination; Metastasis
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Funding
- National Natural Science Foundation of China [91529302, 81572798, 81272749, 81672822]
- Key Projects in the National Science & Technology Pillar Program of China [2014BAI09B03]
- Shanghai Jiao Tong University School of Medicine [BXJ201706]
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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.
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