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

摘要

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.