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LncRNA UCID Promotes Hepatocellular Carcinoma Metastasis via Stabilization of Snail

Authors Yuan S, Si W, Zhuang K, Li Y, Zhang Y, Liu J, Yang L, Zhang X

Received 20 August 2020

Accepted for publication 27 November 2020

Published 28 January 2021 Volume 2021:14 Pages 725—736

DOI https://doi.org/10.2147/OTT.S277951

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Leo Jen-Liang Su


Shanshan Yuan,1,2,* Wangli Si,2,* Kun Zhuang,2 Yijun Li,2 Yanting Zhang,2 Jiaming Liu,2 Li Yang,3 Xin Zhang2

1Department of Gastroenterology, The Affiliated Xi’an Central Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Gastroenterology, Xi’an Central Hospital, Xi’an, Shaanxi, People’s Republic of China; 3Department of Ultrasonography, The Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Li Yang
Department of Ultrasonography, The Affiliated Children’s Hospital of Xi’an Jiaotong University, No. 69, Xijuyuan Lane, Xi’an, Shaanxi, People’s Republic of China
Tel +86-29-87692073
Email liyangscience@21cn.com
Xin Zhang
Department of Gastroenterology, Xi’an Central Hospital, No. 161, Xiwu Road, Xi’an, Shaanxi, People’s Republic of China
Tel +86-29-62812284
Email zhangxin_1121@21cn.com

Background: LncRNAs are functional regulators in tumor progression which act by regulating mRNAs in multiple types of cancer. However, the effect of lnc-UCID on hepatocellular carcinoma (HCC) metastasisremains unclear.
Methods: Lnc-UCID expression was quantified in HCC tissues and HCC cell lines by qRT-PCR. HCC cell lines with lnc-UCID knockdown were established by lentivirus transduction. The migration and invasion abilities of HCC cells were analyzed by Transwell and wound-healing assays. Protein expression of epithelial–mesenchymal transition (EMT)-related factors was examined by Western blot assay. Dual-luciferase assays and actinomycin D treatment were conducted to explore the relationship between lnc-UCID and Snail mRNA. The direct interaction between lnc-UCID and Snail mRNA was subjected to quantification analysis by biotinylated lnc-UCID pulldown assays. Pearson’s correlation coefficient was used to analyze correlations between lnc-UCID and Snail expression level in clinical samples. Rescue experiments were performed to uncover the role of Snail in the HCC metastasis process.
Results: Lnc-UCID was upregulated in human HCC tissues and HCC cell lines. Lnc-UCID promoted the cells’ mobility and invasiveness by enhancing the EMT process of HCC cells. The expression of Snail positively correlated with lnc-UCID abundance, and the interaction between lnc-UCID and Snail mRNA prevented miR-122, miR-203, miR-30b, miR-34a or miR-153 binding to the 3ʹ-UTR of Snail. Transfection of Snail greatly rescued the migration and invasion of HCC cells.
Conclusion: Lnc-UCID was upregulated in clinical HCC samples and directly interacted with Snail mRNA to enhance the stability of Snail mRNA, thus promoting the EMT process to accelerate HCC metastasis.

Keywords: hepatocellular carcinoma, HCC, long non-coding RNA, lnc-UCID, Snail, metastasis

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