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
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
Department of Gastroenterology, Xi’an Central Hospital, No. 161, Xiwu Road, Xi’an, Shaanxi, People’s Republic of China
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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