title: Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway.
abstract: 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.
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Medical College, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Hou-Qun
authors.initials: HQ
authors.lastname: Ying
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Bang-Shun
authors.initials: BS
authors.lastname: He
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Pan
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Qi-Wen
authors.initials: QW
authors.lastname: Deng
authors.affiliation: Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Shu-Kui
authors.initials: SK
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: C575482:MIRN216 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C515159:UCA1 RNA, human; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGFR1; UCA1; hepatocellular carcinoma; lncRNA; miR-216b