circ-E2F3 drives ovarian cancer progression via the miR-1305/STAT3 axis through modulation of ferroptosis

Ovarian cancer (OC) remains the most lethal gynecologic malignancy, with approximately 75% of patients experiencing recurrence within 18-24 months and facing poor clinical outcomes. Accumulating evidence demonstrates that circular RNAs (circRNAs) play crucial roles in OC development and that ferroptosis serves as a novel tumor suppressor mechanism. This study aimed to elucidate the functional role and underlying molecular mechanisms of circ-E2F3 in OC progression. We identified significant upregulation of circ-E2F3 (2-3.5 fold increase) and downregulation of miR-1305 (0.3-0.7 fold decrease) in OC cells compared to normal controls. Circ-E2F3 knockdown induced ferroptosis and significantly inhibited proliferation and invasion capabilities in OC cells. Furthermore, bioinformatics analysis combined with dual-luciferase reporter, RNA pull-down, and AGO2-RIP assays demonstrated functional interactions between circ-E2F3 and miR-1305, as well as between miR-1305 and signal transducer and activator of transcription 3 (STAT3). Rescue experiments showed that the tumor-suppressive effects of circ-E2F3 knockdown were partially reversed by miR-1305 silencing or STAT3 overexpression. Collectively, our findings demonstrate that circ-E2F3 upregulates STAT3 expression by sequestering miR-1305, thereby relieving miR-1305-mediated suppression of STAT3 and subsequently promoting the malignancy in OC cells. These results suggest that targeting the circ-E2F3/miR-1305/STAT3 axis may represent a promising therapeutic strategy for OC treatment.