Matrine inhibits hepatocellular carcinoma cell malignancy through the circ_0013290/miR-139-5p/MMP16 pathway

Abstract

Background. Previous studies have shown the anticancer effect of Matrine on hepatocellular carcinoma (HCC); however, the underlying mechanism is still indistinct. Methods. The expression of circular RNA_0013290 (circ_0013290), microRNA-139-5p (miR-139-5p), matrix metallopeptidase 16 (MMP16), CyclinD1 and N-cadherin was analyzed by quantitative real-time polymerase chain reaction, Western blotting or immuno-histochemistry assay. Cell viability, proliferation, apoptosis, invasion and tube formation were analyzed by cell counting kit-8, 5-Ethynyl-2’-deoxyuridine, flow cytometry analysis, transwell invasion and tube formation assays, respectively. The associations among circ_0013290, miR-139-5p and MMP16 were predicted by starbase online database, and identified by dual-luciferase reporter and RNA pull-down assays. A xenograft mouse model assay was conducted to disclose the effects of circ_0013290 and Matrine on tumor tumorigenesis in vivo. Results. Circ_0013290 and MMP16 expression were significantly upregulated, while miR-139-5p was downregulated in HCC tissues and cells compared with the matched normal liver tissues and cells. Matrine treatment inhibited HCC cell proliferation, invasion and tube formation but induced cell apoptosis, accompanied by the decrease of CyclinD1 and N-cadherin expression; however, these effects were counteracted when circ_0013290 expression was increased. MiR-139-5p depletion or MMP16 introduction relieved Matrine-induced effects in HCC cells. The regulation of circ_0013290 toward HCC cell processes involved MMP16. With respect to the mechanism, circ_0013290 acted as a miR-139-5p sponge, and miR-139-5p targeted MMP16 in HCC cells. Besides, circ_0013290 regulated MMP16 expression through miR-139-5p. Further, circ_0013290 depletion enhanced the inhibitory effects of Matrine on tumor tumorigenesis. Conclusion. Matrine inhibited HCC cell malignancy through the circ_0013290/miR-139-5p/MMP16 pathway, suggesting that Matrine is a potential therapeutic agent for HCC