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circSMAD2 inhibits the epithelial–mesenchymal transition by targeting miR-629 in hepatocellular carcinoma

Authors Zhang XW, Luo P, Jing W, Zhou H, Liang CZ, Tu JC

Received 24 November 2017

Accepted for publication 27 January 2018

Published 16 May 2018 Volume 2018:11 Pages 2853—2863

DOI https://doi.org/10.2147/OTT.S158008

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai


Xianwei Zhang,1 Ping Luo,1 Wei Jing,1 Hu Zhou,2 Chunzi Liang,1 Jiancheng Tu1

1Department of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

Background: Circular RNAs (circRNAs) are a class of widely distributed non-coding RNAs, which drew little attention for decades. Recent studies show that circRNAs are involved in cancer progression.
Methods: The circSMAD2 expression in HCC and adjacent non-tumor tissues was measured by quantitative real-time polymerase chain reaction, and the biological function of circSMAD2 was explored by proliferation, apoptosis, migration, invasion, and Western blot assays. Next, the dual-luciferase reporter assay was performed to identify the target miRNA of circSMAD2. Finally, circSMAD2 and its target miRNA were co-transfected in HCC cells to investigate their relationship to HCC progression.
Results: In this study, we found that circRNA SMAD2 (circSMAD2) expression was downregulated in hepatocellular carcinoma (HCC) tissues (P = 0.014) compared to the adjacent non-tumor tissues and markedly associated with the differentiation degree of the HCC tissues (P < 0.001). The in vitro experiments showed that overexpressed circSMAD2 inhibited the migration, invasion, and epithelial–mesenchymal transition (EMT) in HCC cells. Bioinformatics predicted that miR-629 is a potential target of circSMAD2, and the dual-luciferase reporter assay verified that miR-629 directly bound circSMAD2. In addition, we found that overexpression of circSMAD2 suppressed the expression of miR-629 in HCC cells, whereas knockdown of circSMAD2 upregulated the expression of miR-629. Furthermore, co-transfection of miR-629 mimics with circSMAD2 reversed the circSMAD2 effects of inhibiting the migration, invasion, and EMT of HCC cells.
Conclusion: Altogether, our data support that circSMAD2 inhibits the migration, invasion, and EMT of HCC cells by targeting miR-629.

Keywords: circular RNA, circSMAD2, hepatocellular carcinoma, epithelial–mesenchymal transition, microRNA-629

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