Circular RNA 0016142 Knockdown Induces Ferroptosis in Hepatocellular Carcinoma Cells via Modulation of the MicroRNA-188-3p/Glutathione Peroxidase 4 Axis.

ABSTRACT

Hepatocellular carcinoma (HCC) has high incidence and mortality rates, and it is characterized by invasiveness, poor prognosis, and limited treatment opportunities. The objective of our research was to assess the role of circ_0016142 in HCC. The ferroptosis inducer RSL3 and the iron chelator deferoxamine were used to treat cells to induce or inhibit ferroptosis, respectively, and cell viability and proliferation were assessed in Hep3B and HA22T cells by CCK8 and EdU assays, respectively. ROS, MDA, GSH, and Fe2+ levels were determined using commercial kits. RT-qPCR and western blotting were performed to determine the relative expression levels of entities of interest. Dual-luciferase reporter and RNA pull-down assays were performed to assess the relationship between circ_0016142/GPX4 and miR-188-3p. The results showed that circ_0016142/GPX4 was overexpressed, whereas miR-188-3p was downregulated in HCC. Circ_0016142 silencing reduced cell proliferation and GSH levels and increased ROS, MDA, and Fe2+ levels in HCC cells, and this was reversed by the miR-188-3p inhibitor. GPX4-overexpression abolished the effect of miR-188-3p mimic in HCC cells. In conclusion, circ_0016142 silencing suppressed HCC cell proliferation by inducing ferroptosis via the miR-188-3p/GPX4 axis.