CircBNC2 affects epithelial ovarian cancer progression through the miR-223-3p/LARP4 axis

Abstract

Epithelial ovarian cancer (EOC) is one of the most serious cancer. Circular RNA BNC2 (circBNC2) expression was decreased in EOC tissues. However, the molecular mechanism of circBNC2 remains unknown. The expression of circBNC2, microRNA-223-3p (miR-223-3p), and La-related proteins 4 (LARP4) were detected by quantitative real-time fluorescence PCR (qRT-PCR). A series of in-vitro experiments were designed to explore the function of circBNC2 in EOC cells and the regulatory mechanism between circBNC2 and miR-223-3p and LARP4 in EOC cells. Western blot examined the protein levels of Snail1, Slug, and LARP4. The relationship between miR-223-3p and circBNC2 or LARP4 was verified by Dual-luciferase reporter assays. The xenotransplantation model was established to study the role of circBNC2 in vivo. The expression of circBNC2 and LARP4 was decreased in EOC tissues, while the expression of miR-223-3p was increased. CircBNC2 can sponge miR-223-3p, and LARP4 is the target of miR-223-3p. In-vitro complement experiments showed that overexpression of circBNC2 significantly decreased the malignant behavior of EOC, while co-transfection of miR-223-3p mimics partially upregulated this change. In addition, LARP4 knockdown increased the proliferation, migration, and invasion of EOC cells inhibited by miR-223-3p inhibitor. Mechanically, circBNC2 regulates LARP4 expression in EOC cells by spongy miR-223-3p. In addition, in-vivo studies have shown that overexpression of circBNC2 inhibits tumor growth. Overexpression of circBNC2 decreased proliferation, migration, and invasion of EOC cells by regulating the miR-223-3p/LARP4 axis, suggesting that circBNC2/miR-223-3p/LARP4 axis may be a potential regulatory mechanism for the treatment of EOC.