Hsa_circ_0001445 works as a cancer suppressor via miR-576-5p/SFRP1 axis regulation in ovarian cancer

Background: Ovarian cancer (OC) has high mortality and morbidity. Circular RNA (circRNA) can deeply impact the tumor occurrence and growth. The pathogenic activity of one particular circRNA, hsa_circ_0001445 (hcR1445), in OC remains unclear and was therefore analyzed in this study.

Methods: Human OC tissue specimens and cell lines (SKOV3, HO8910, and OVCAR8) were used to examine the levels of hcR1445 and the microRNA miR-576-5p using polymerase chain reaction. The 5-ethynyl-2'-deoxyuridine, flow cytometry, cellular scratch test, CCK-8, and Transwell migration assays were used to examine the biological activities of hcR1445 and miR-576-5p on cell apoptosis, invasion, migration, and proliferation in OC cells. Protein expression of WNT/β-catenin and secreted frizzled-related protein 1 (SFRP1) were tested using Western blot analysis. The potential interactions of miR-576-5p/SFRP1 and hcR1445/miR-576-5p were evaluated using a dual-luciferase report assay. The effect of hcR1445 on OC growth and metastasis was further determined using an OC tumor xenograft model in vivo.

Results: hcR1445 level was declined in OC cells and tissues. hcR1445 reduced cellular invasion, proliferation, and migration by blocking the ability of miR-576-5p to upregulate SFRP1 expression and consequently prohibit WNT/β-catenin signal transduction. hcR1445 upregulation suppressed OC growth, development, and intraperitoneal metastasis in vivo.

Conclusion: hcR1445 acts an antioncogene by targeting the miR-576-5p/SFRP1 axis and blocking OC progression and development. Thus, hcR1445 may be employed as an indicator or a possible therapeutic target in OC patients.