Circ_0021573 acts as a competing endogenous RNA to promote the malignant phenotypes of human ovarian cancer cells

Abstract

Circular RNAs (circRNAs) have been reported to be implicated in the tumorigenesis and progression of ovarian cancer. Here, the study was designed to explore the activity of human circ_0021573 in ovarian cancer pathogenesis and its regulation through the competing endogenous RNA (ceRNA) crosstalk. Circ_0021573, microRNA (miR)- 936, and cullin 4B (CUL4B) were quantified by qRT-PCR and western blot. Cell proliferation ability was detected by XTT, 5-Ethynyl-2'-Deoxyuridine (EdU), and colony formation assays. Cell apoptosis, migration, and invasion were assessed by flow cytometry, wound-healing, and transwell assays, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-936 and circ_0021573 or CUL4B 3'UTR. Xenograft studies were applied to assess the role of circ_0021573 in tumor growth. Our data showed that circ_0021573 expression is enhanced in human ovarian cancer. Inhibition of circ_0021573 impedes cell proliferation, migration, and invasion and promotes apoptosis in vitro, as well as diminishes tumor growth in vivo. Mechanistically, circ_0021573 contains a miR-936 binding site, and miR-936 is a relevant mediator of circ_0021573 regulation. MiR-936 direct targets and inhibits CUL4B. MiR-936-mediated suppression of CUL4B hinders cell proliferation, migration, and invasion and accelerates apoptosis in vitro.. These data suggested that circ_0021573 might promote the malignant phenotypes of ovarian cancer cells by functioning as a ceRNA for miR-936 to induce CUL4B, which provided a promising target for the prevention and inhibition of ovarian cancer.

Keywords: CUL4B; Circ_0021573; MiR-936; Ovarian cancer.