Abstract
Hepatocellular carcinoma (HCC) is a highly aggressive, solid malignancy that has a poor prognosis. Long non-coding RNAs (lncRNAs) have been found to be dysregulated in various cancers, including HCC. However, the molecular mechanism involving lncRNAs in HCC remains largely unknown. In this study, lncRNAs differentially expressed between HCC and corresponding non-cancerous tissue were identified by microarray analysis. A specific differentially expressed lncRNA UBE2CP3 (ubiquitin conjugating enzyme E2 C pseudogene 3) was identified. LncRNA UBE2CP3 was frequently up-regulated in HCC samples as assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) experiments. Clinical data showed that high levels of lncRNA UBE2CP3 were correlated with poor prognosis in HCC patients. Functional studies demonstrated that over-expression of lncRNA UBE2CP3 promoted cell invasion and migration in vitro and in vivo. Mechanistically, enhanced expression of lncRNA UBE2CP3 increased the expression of Snail1 and N-cadherin, but decreased the expression of E-cadherin, thus promoting the process of epithelial to mesenchymal transition (EMT) and finally inducing cell invasion and migration. Furthermore, serum levels of lncRNA UBE2CP3 were increased in HCC patients and decreased after surgery. Our results suggest that lncRNA UBE2CP3 promotes the metastasis of HCC and that serum lncRNA UBE2CP3 may be a new biomarker for the diagnosis of HCC.
Highlights
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy that is associated with a poor prognosis [1]
The in situ hybridization (ISH) studies performed with 85 paraffin-embedded HCC specimens from Cohort 2 confirmed the up-regulation of long noncoding RNA (lncRNA) UBE2CP3 in HCC and suggested that lncRNA UBE2CP3 was localized to the cytoplasm of HCC tissue (P < 0.001; Figure 1C and 1D).These findings indicate that lncRNA UBE2CP3 is frequently up-regulated in HCC
The results showed that lncRNA UBE2CP3 expression (95%confidence interval (CI):1.333-5.540; P = 0.006) was an independent prognostic factor for HCC patients (Table 3)
Summary
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy that is associated with a poor prognosis [1]. The chief reasons responsible for the poor prognosis are the high rate of tumor recurrence and distant metastasis after hepatic resection [2]. Mounting evidence has linked dysregulations of lncRNAs to cancers. LncRNAs may have oncogenic or tumor suppressive roles in the regulation of multiple biological processes such as development, differentiation and carcinogenesis [6,7,8]. LncRNAs are reported to play regulatory roles in cancer recurrence and metastasis and contribute to tumorigenesis and tumor progression [9,10,11]. To date, only a limited number of lncRNAs have been studied in the onset and progression of HCC
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