The Investigation of the SKA3 Circular RNA Role in the Ovarian Cancer Progression

Circular RNAs (circRNAs) are becoming increasingly more recognized in cancer biology as novel biomarkers due to their high stability as well as tissue- and developmental stage-specific expression. Despite massive improvements made in treatments, ovarian cancer (OC) still is considered one of the deadliest types of gynecologic cancers. SKA3 gene is known for its role in cell proliferation and apoptosis. A circRNA-seq study conducted by our collaborators suggests that circSKA3 is upregulated in the most aggressive subtype of OC, high-grade serous carcinoma (HGSC). Our study showed that circSKA3 levels were higher in HGSC than in tumors with low malignant potential (LMP). Using functional assays, we demonstrated that overexpression of circSKA3 promoted, while the silence of cirSKA3 suppressed, proliferation, migration, and invasion in OVAR3, and CAOV3 cells derived from HGSC. We found that silencing of circSKA3 resulted in an increase in miR-383-5p levels and upregulation of a miR-383-5p target gene, lactate dehydrogenase-A (LDHA). Interestingly, overexpression of miR-383-5p or silencing of LDHA reversed the effects of circSKA3 in cell invasion. These findings suggest that circSKA3 promotes HGSC development by sponging miR-383-5p to induce LDHA expression and that circSKA3 may be used as a diagnostic or therapeutic target for HGSC in the future.