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CircBNC2 affects epithelial ovarian cancer progression through the miR-223-3p/ LARP4 axis
Meirong Lu1, Bianrong Gong2, Yi Wang2
1Department of Gynaecology, Xi'an International Medical Center Hospital.
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.
Insights
Circular RNA BNC2 (circBNC2) inhibits epithelial ovarian cancer (EOC) progression by sponging miR-223-3p, thereby upregulating La-related protein 4 (LARP4). This circBNC2/miR-223-3p/LARP4 axis offers a potential therapeutic target for EOC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Epithelial ovarian cancer (EOC) is a significant health concern with complex molecular underpinnings.
- Circular RNAs (circRNAs) are emerging as critical regulators in various cancers, but their role in EOC is not fully understood.
- The specific function and mechanism of circRNA BNC2 (circBNC2) in EOC remain largely unknown.
Purpose of the Study:
- To investigate the expression levels of circBNC2, microRNA-223-3p (miR-223-3p), and La-related protein 4 (LARP4) in EOC.
- To elucidate the molecular mechanism by which circBNC2 influences EOC cell behavior.
- To explore the regulatory axis involving circBNC2, miR-223-3p, and LARP4 in EOC.
Main Methods:
- Quantitative real-time fluorescence PCR (qRT-PCR) to measure RNA expression.
- In-vitro cell-based assays to assess cell proliferation, migration, and invasion.
- Western blot to analyze protein expression levels.
- Dual-luciferase reporter assays to confirm molecular interactions.
- Xenotransplantation models in vivo to evaluate tumor growth.
Main Results:
- circBNC2 and LARP4 expression were decreased, while miR-223-3p expression was increased in EOC tissues.
- circBNC2 acts as a sponge for miR-223-3p, and LARP4 is a direct target of miR-223-3p.
- Overexpression of circBNC2 suppressed EOC cell malignant behaviors in vitro and tumor growth in vivo.
- The suppressive effects of circBNC2 were partially reversed by miR-223-3p mimics, and LARP4 knockdown counteracted the inhibition by miR-223-3p inhibitors.
Conclusions:
- circBNC2 inhibits EOC progression by regulating the miR-223-3p/LARP4 axis.
- circBNC2 acts as a tumor suppressor in EOC through this molecular pathway.
- The circBNC2/miR-223-3p/LARP4 axis represents a potential therapeutic strategy for epithelial ovarian cancer.
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