CircWHSC1 Promotes Ovarian Cancer Progression by Regulating MUC1 and HTERT Through Sponging MiR-145 and MiR-1182

Background: Circular RNAs are key regulators in human cancers, however, there is a lack of studies on circRNAs' specific functions in ovarian cancer.

Methods: Our study used qRT-PCR to detect the differentially expressed circRNAs between normal ovaries and ovarian cancer tissues. Cell function experiments were performed to verify the role of overexpression and silence of circWHSC1, including MTT assay, cell apoptosis assay, wound healing and Matrigel-coated Transwell assay. In vivo tumorigenesis model was constructed by subcutaneous injection in nude mice. Bioinformatics analysis predicted the possible binding sites of circWHSC1 with miRNAs, and confirmed with dual-luciferase reporter assay and RNA pull-down assay. The exosomes were extracted with ultracentrifugation. HE staining was also used to detect morphology of nude mice peritoneum.

Results: We found that circWHSC1 was up-regulated in ovarian cancer tissues, and circWHSC1 expression was higher in moderate & poor differentiation ovarian cancer tissues than in well differentiation ovarian cancer tissues. Overexpression of circWHSC1 increased cell proliferation, migration and invasion, and inhibited cell apoptosis. Silence of circWHSC1 exerted the opposite effects. Additionally, circWHSC1 could sponge miR-145 and miR-1182 and up-regulate the expression of downstream targets MUC1 and hTERT. Exosomal circWHSC1 can be transferred to peritoneal mesothelial cells and promotes peritoneal dissemination.

Conclusions: Our study demonstrates the highly expressed circWHSC1 in ovarian cancer promotes tumorigenesis by sponging miR-145 and miR-1182, and its exosome forms induce tumor metastasis through acting on peritoneal mesothelium.