Circ_0000471 Suppresses the Progression of Ovarian Cancer Through Mediating Mir-135b-5p/dusp5 Axis

Background: Ovarian cancer (OC) is a common gynecologic cancer with high incidence and mortality. We attempted to investigate the role of circular RNA_0000471 (circ_0000471) in OC progression and its associated mechanism.

Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay were conducted to measure RNA and protein expression, respectively. Cell proliferation was analyzed by Cell Counting Kit-8 (CCK8) assay, colony formation assay, and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was assessed by flow cytometry. Cell migration and invasion were analyzed by wound healing assay and transwell assay, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the target relationships. Xenograft tumor model was established to assess the role of circ_0000471 on tumor growth in vivo.

Results: Circ_0000471 expression was down-regulated in OC tissues and cell lines. Circ_0000471 overexpression blocked the proliferation, migration, and invasion and triggered the apoptosis of OC cells. Circ_0000471 served as a molecular sponge for microRNA-135b-5p (miR-135b-5p), and circ_0000471 overexpression-mediated anti-tumor influences in OC cells were largely reversed by the overexpression of miR-135b-5p. Dual specificity phosphatase 5 (DUSP5) was a target of miR-135b-5p, and miR-135b-5p silencing-induced anti-tumor effects were largely counteracted by the interference of DUSP5. Circ_0000471 increased DUSP5 expression by sponging miR-135b-5p in OC cells. Circ_0000471 overexpression restrained the growth of xenograft tumors in vivo.

Conclusion: Overexpression of circ_0000471 inhibited OC development by targeting miR-135b-5p/DUSP5 axis, indicating that circ_0000471 may be a new potential target for OC treatment.