Department of Gynaecology, Xi'an International Medical Center Hospital.
Department of Gynaecology, Xi'an High Tech Hospital, Xi'an.
Anticancer Drugs. 2023 Mar 1;34(3):384-394. doi: 10.1097/CAD.0000000000001423. Epub 2022 Nov 17.
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.
上皮性卵巢癌 (EOC) 是最严重的癌症之一。环状 RNA BNC2 (circBNC2) 在 EOC 组织中的表达降低。然而，circBNC2 的分子机制尚不清楚。通过实时荧光定量 PCR (qRT-PCR) 检测 circBNC2、microRNA-223-3p (miR-223-3p) 和 La 相关蛋白 4 (LARP4) 的表达。设计了一系列体外实验来探索 circBNC2 在 EOC 细胞中的功能以及 circBNC2 与 miR-223-3p 和 EOC 细胞中 LARP4 之间的调节机制。Western blot 检测了 Snail1、Slug 和 LARP4 的蛋白水平。通过双荧光素酶报告基因检测验证了 miR-223-3p 与 circBNC2 或 LARP4 的关系。建立异种移植模型研究 circBNC2 在体内的作用。EOC 组织中 circBNC2 和 LARP4 的表达降低，而 miR-223-3p 的表达增加。CircBNC2 可以海绵 miR-223-3p，LARP4 是 miR-223-3p 的靶标。体外互补实验表明，circBNC2 的过表达显著降低了 EOC 的恶性行为，而共转染 miR-223-3p 模拟物部分上调了这种变化。此外，LARP4 敲低增加了 miR-223-3p 抑制剂抑制的 EOC 细胞的增殖、迁移和侵袭。机械地，circBNC2 通过海绵 miR-223-3p 调节 EOC 细胞中的 LARP4 表达。此外，体内研究表明过表达 circBNC2 抑制肿瘤生长。circBNC2 通过调节 miR-223-3p/LARP4 轴降低 EOC 细胞的增殖、迁移和侵袭，表明 circBNC2/miR-223-3p/LARP4 轴可能是治疗 EOC 的潜在调节机制。
