Long noncoding RNA UCA1 promotes tumour metastasis by inducing GRK2 degradation in gastric cancer

• Published in: Cancer letters 2017-11, Vol.408, p.10-21
• Main Authors: Wang, Zhen-qiang, He, Chang-yu, Hu, Lei, Shi, Hong-peng, Li, Jian-fang, Gu, Qin-long, Su, Li-ping, Liu, Bing-ya, Li, Chen, Zhu, Zhenggang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; b-Adrenergic-receptor kinase; Cbl protein; Cell Movement; Cell Proliferation; Ethics; Experiments; G-Protein-Coupled Receptor Kinase 2 - genetics; G-Protein-Coupled Receptor Kinase 2 - metabolism; Gastric cancer; Gelatinase B; Gene Expression Regulation, Neoplastic; Humans; Kinases; lncRNA; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; Mortality; Post-transcription; Proteins; Proteolysis; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Rodents; Signal Transduction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Transcription; Tumor Cells, Cultured; Tumors; Ubiquitination; UCA1; Wound healing; Xenograft Model Antitumor Assays
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.08.013

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. •LncRNA UCA1 promotes the migration and invasiveness of GC cells in vitro and tumour metastasis in vivo.•LncRNA UCA1 increases GC migration and invasion via the activation of the ERK-MMP9 signalling pathway.•LncRNA UCA1 interacts with GRK2 and promotes GRK2 degradation via ubiquitination.•LncRNA UCA1 enhances Cbl-c-mediated ubiquitination.•LncRNA UCA1 regulates ERK-MMP9 signalling via downregulating GRK2.