Circular RNA circMAN1A2 promotes ovarian cancer progression through the microRNA- 135a-3p/IL1RAP/pTAK1 pathway

Background: Ovarian cancer (OC) is the most lethal malignancy in women owing to its diagnosis only at the advanced stage. Elucidation of its molecular pathogenesis could reveal new tumor markers and targets for therapy. Circular RNAs (circRNAs) are stable, conserved, and functional biomolecules that can be used as effective biomarkers for various cancers. In this study, a potential circRNA related to early diagnosis of OC, circMAN1A2, was analyzed. Methods Overexpression/knockdown of circMAN1A2 in OC cells was used to decipher its effects on cell proliferation with CCK8, EdU, cell cycle, clone formation and wound healing assay. RNA pull-down, RIP and Dual luciferase assay were used to explain the underlying mechanism of circMAN1A2 regulation of OC cell proliferation. In vivo, the effect of circMAN1A2 in OC was evaluated using nude mouse xenograft experiments. Results circMAN1A2 was highly expressed in OC and promoted proliferation, clone formation, and tumorigenicity of OC cells. In addition, we found that circMAN1A2 acts as a sponge for microRNA (miR)-135a-3p; miR-135a-3p directly targets the 3′ untranslated region of IL1RAP in OC cells, thereby regulating the phosphorylation of TAK1, which results in promotion of OC cell growth. Therefore, circMAN1A2 promotes OC cell proliferation by inhibiting the miR-135a-3p/IL1RAP/pTAK1 axis. Conclusion circMAN1A2 may be a biomarker for early detection of OC and a target for subsequent therapy.