Abstract
Purpose
Long non-coding RNA (LncRNA) urothelial carcinoma-associated 1 (UCA1) is reported to be dysregulated in hepatocellular carcinoma (HCC) progression. However, the functions of UCA1 in HCC still need further study. The aim is to detect the role of UCA1 involving in HCC cells proliferation and invasion, and epithelial–mesenchymal transition (EMT).
Methods
The quantitative real-time PCR was used to detect the UCA1 and miR-203 expression levels in 60 cases’ HCC tissues and adjacent normal tissues. Western blotting analysis was performed to detect the EMT markers E-cadherin, Vimentin and transcription factor Snail1, Snail2 expression. Luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assays were used to evaluate whether miR-203 was a target of UCA1.
Results
Our results showed that UCA1 was markedly upregulated in HCC tissues and higher UCA1 expression in HCC was positively associated with tumor size, vascular invasion and American Joint Committee on Cancer (AJCC) stage (P < 0.05). Furthermore, gain-of-function and loss-of-function analysis showed that UCA1 knockdown inhibited HCC cells proliferation and invasion in vitro and xenograft tumour growth in vivo. Moreover, UCA1 overexpression promoted cell epithelial–mesenchymal transition (EMT) in HCC via effectively sponging to miR-203 and thereby activating the expression of transcription factor Snail2.
Conclusions
Our results identified that UCA1/miR-203/Snail2 pathway might involve in HCC progression. Inhibition of UCA1 acted as a promising therapeutic target for HCC patients.
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Acknowledgements
We thanks for Department of Pathology of First Clinical Medical College of Fujian Medical University for its generous help. This research was supported by Foundation of LongYan Medical Science and Technique Key Program (Grant No. 2013LY57).
Author contributions
T-HY and J-HJ contributed in study concept and design, execution of experiments and writing of the manuscript. RMY, YG, and W-LZ performed statistical analysis and interpretation of data. S-WL, H-XQ, and Z-PL collected tissue samples and clinical data and performed the experiments. J-NX, T-HY and J-HJ revised the manuscript.
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The authors declare no conflict of interest.
Ethical approval
The study was approved by the Local Ethical Committee of Longyan Humanity Hospital (Longyan, Fujian, China) and complied with the Declaration of Helsinki. All procedures performed in this study were in accordance with the 1964 Helsinki Declaration and its later amendments.
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Written informed consent was obtained from all patients included in the study.
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J.-N. Xiao and T.-H. Yan are contributed equally to this work.
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Xiao, JN., Yan, TH., Yu, RM. et al. Long non-coding RNA UCA1 regulates the expression of Snail2 by miR-203 to promote hepatocellular carcinoma progression. J Cancer Res Clin Oncol 143, 981–990 (2017). https://doi.org/10.1007/s00432-017-2370-1
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DOI: https://doi.org/10.1007/s00432-017-2370-1