Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway
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Feng Wang1,*, Hou-Qun Ying2,*, Bang-Shun He1, Yu-Qin Pan1, Qi-Wen Deng1, Hui-Ling Sun3, Jie Chen3, Xian Liu1, Shu-Kui Wang1
1Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
2Medical college, Southeast University, Nanjing, Jiangsu, China
3Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China
*These authors have contributed equally to this work
Shu-Kui Wang, e-mail: firstname.lastname@example.org
Keywords: hepatocellular carcinoma, lncRNA, UCA1, miR-216b, FGFR1
Received: November 17, 2014 Accepted: January 26, 2015 Published: February 11, 2015
The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated, which plays an important role in the progression of several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of hepatocellular carcinoma (HCC) remain unclear. Herein, we found that UCA1 was aberrantly upregulated in HCC tissues and associated with TNM stage, metastasis and postoperative survival. UCA1 depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Furthermore, UCA1 could act as an endogenous sponge by directly binding to miR-216b and downregulation miR-216b expression. In addition, UCA1 could reverse the inhibitory effect of miR-216b on the growth and metastasis of HCC cells, which might be involved in the derepression of fibroblast growth factor receptor 1 (FGFR1) expression, a target gene of miR-216b, and the activation of ERK signaling pathway. Taken together, our data highlights the pivotal role of UCA1 in the tumorigenesis of HCC. Moreover, the present study elucidates a novel lncRNA-miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling pathway in HCC, which may help to lead a better understanding the pathogenesis of HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this deadly disease.
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