Oxidative Medicine and Cellular Longevity Hsa_circ_0013731 mediated by E2F1 inhibits ferroptosis in hepatocellular carcinoma cells by sponging miR-877-3p and targeting SLC7A11

Abstract Background: The regulatory loop between circular RNAs and microRNAs has a vital role in cell death. Ferroptosis is the form of iron-dependent cell death, which is distinct from necroptosis and apoptosis. Increasing evidences showed that ferroptosis is an important form of cell death in hepatocellular carcinoma.Methods: Real-time PCR were used to examine the expression level of circ_0013731 in hepatocellular carcinoma tissues. Edu and colony formation were performed to detect the cell proliferation. A luciferase reporter assay was used to determine the relationship between circ_0013731, miR-877-3p and SLC7A11. ChIP-qPCR assays were performed to examine the potential binding of E2F1 to the circ_0013731 promoter. Iron Assay Kit (Sigma Aldrich) was used to detect total iron or Fe2+. C11 BODIPY 581/591 staining and flow cytometer were used to examine the Lipid ROS. The role of circ_0013731 was examined in xenograft tumors model. Results: We revealed that the expression level of circ_0013731 was elevated in hepatocellular carcinoma. Moreover, E2F1 promote the transcription of circ_0013731. Overexpression of circ_0013731 promoted cell growth and inhibited ferroptosis in SMMC-7721 and QGY-7703 in vitro. miR-877-3p was proved as the direct target of circ_0013731. Then, inhibition of miR-877-3p enhanced cell growth and inhibited ferroptosis. Further mechanism research demonstrated that circ_0013731 upregulated the expression level of SLC7A11 by sponging miR-877-3p. Finally, circ_0013731 promoted HCC growth via miR-877-3p/ SLC7A11 axis in vivo.Conclusions: Our data reveal that circ_0013731 mediated by E2F1 facilitates cell growth and suppressed the ferroptosis via miR-877-3p/ SLC7A11 axis in hepatocellular carcinoma. Therefore, circ_0013731 could be acted as potential therapeutical target for hepatocellular carcinoma.