Circ-SPECC1 modulates TGFβ2 and autophagy under oxidative stress by sponging miR-33a to promote hepatocellular carcinoma tumorigenesis.

Circular RNAs (circRNAs) play vital roles in the pathogenesis and development of multiple cancers, including hepatocellular carcinoma (HCC). Nevertheless, the regulatory mechanisms of circ-SPECC1 in HCC remain poorly understood. In our study, we found that circ-SPECC1 was apparently downregulated in H2 O2 -treated HCC cells. Additionally, knockdown of circ-SPECC1 inhibited cell proliferation and promoted cell apoptosis of HCC cells under H2 O2 treatment. Moreover, circ-SPECC1 inhibited miR-33a expression by direct interaction, and miR-33a inhibitor partially reversed the effect of circ-SPECC1 knockdown on proliferation and apoptosis of H2 O2 -treated HCC cells. Furthermore, TGFβ2 was demonstrated to be a target gene of miR-33a and TGFβ2 overexpression rescued the phenotypes of HCC cells attenuated by miR-33a mimics. Meanwhile, autophagy inhibition by 3-methyladenine (3-MA) abrogated the effect of miR-33a mimics on proliferation and apoptosis of H2 O2 -treated HCC cells. Finally, knockdown of circ-SPECC1 hindered tumor growth in vivo. In conclusion, our study demonstrated that circ-SPECC1 regulated TGFβ2 and autophagy to promote HCC tumorigenesis under oxidative stress via miR-33a. These findings might provide potential treatment strategies for patients with HCC.