Introduction: Epithelial ovarian cancer is the most lethal gynaecological cancer, with high-grade serous carcinoma (HGSC) being the most prevalent and aggressive subtype. Circular RNA (circRNA) is a class of non-coding RNAs, with a ring-like structure facilitated by the covalent linkage of its 3’ to 5’ end and formed by back-splicing of pre-mRNAs. They function as microRNA (miRNA) sponges but can also interact with proteins. Emerging evidence suggests that circRNAs are potential cancer biomarkers and therapeutic targets.  

Method: RT-qPCR was used to compare circSKA3 levels among HGSC, benign tumors and tumors of low malignant potentials (LMP). Various cell-based assays, including proliferation, migration, invasion, and colony formation, were used to study the effect of circSKA3 overexpression and knockdown in several HGSC lines. Expression levels of predicted circSKA3 binding miRNAs and their target genes were measured by RT-qPCR.

Results: circSKA3 levels were significantly higher in HGSC tumors (n=33) than in serous LMPs (n=28) and benign serous cystadenofibromas (n=16). Overexpression of circSKA3 promoted, while their silencing reduced, cell proliferation, migration, and invasion. Stable overexpression of circSKA3 also increased colony formation.  In addition, circSKA3 reduced miR-383-5p levels but increased the mRNA level of lactate dehydrogenase (LDHA), a target gene of miR-383-5p.

Conclusions: circSKA3 is overexpressed in HGSC and exerts tumor-promoting effects, possibly by sponging miR-383-5p to increase LDHA. These findings suggest a potential role of circSKA3 in promoting HGSC progression