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.
Highlights
Hepatocellular carcinoma (HCC) ranks the sixth most common tumors and the third leading cause of cancer-related mortality worldwide
We found that the expression of urothelial carcinoma-associated 1 (UCA1) in HCC tissues was conspicuously higher than that observed in pair-matched adjacent nontumourous tissues, (P < 0.001, Figure 1B)
Clinicopathological analysis showed that UCA1 was significantly correlated with advanced TNM stage (P < 0.001) and metastasis (P < 0.001); whereas, there was no significant correlation between UCA1 and other clinicopathological characteristics such as gender, age, tumor size, serum AFP level and degree of histological differentiation, (P > 0.05, Table 1)
Summary
Hepatocellular carcinoma (HCC) ranks the sixth most common tumors and the third leading cause of cancer-related mortality worldwide. The majority of the cases occur in Asia and Africa, the incidence of HCC in the United States has been rising over the past three decades and currently represents the fastest growing cause of cancer-related deaths among men [1]. The recent discovery of lncRNAs and the elucidation of their functions have disclosed a new www.impactjournals.com/oncotarget layer of complexity underlying the regulation of gene expression in cancer. Documents have demonstrated that several lncRNAs, such as lncRNA HULC, RERT and HOTTIP/HOXA13, etc., are dysregulated in HCC and closely related to tumorigenesis, metastasis, prognosis, diagnosis, and drug resistance [5,6,7], opening up a new avenue for investigating the occurrence and development molecular mechanisms of HCC
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