Circ_0044520 regulates the progression of laryngeal squamous cell carcinoma via the miR-338-3p/ROR2 axis

Abstract

Background. Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Circular RNA_0044520 (circ_0044520) expression is increased in LSCC. However, the molecular mechanism of circ_0044520 remains unknown. Methods. The expression of circ_0044520, microRNA-338-3p (miR-338-3p) and receptor tyrosine kinase-like orphan receptor 2 (ROR2) were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). Cell viability, cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and flow cytometry assay, respectively. Western blot examined the protein levels of PCNA, Cyclin D1, Bax, Bcl-2 and ROR2 cells. The relationship between miR-338-3p and circ_0044520 or ROR2 was verified by Dual-luciferase reporter assays. The xenotransplantation model was established to study the role of circ_0044520 in vivo. Results. The expression of circ_0044520 and ROR2 was increased in LSCC tissues and cells, while the expression of miR-338-3p was decreased. Circ_0044520 can sponge miR-338-3p, and ROR2 is the target of miR338-3p. In vitro complement experiments showed that knockdown of circ_0044520 significantly inhibited malignant behavior of LSCC, while co-transfection of miR-338-3p inhibitor partially up-regulated this change. In addition, miR-338-3p can inhibit the proliferation of LSCC cells, while co-transfection of overexpression of ROR2 can partially reverse this change. Mechanically, circ_0044520 regulates ROR2 expression in LSCC cells by sponging miR-338-3p. In addition, in vivo studies have shown that down-regulation of circ_0044520 inhibits tumor growth. Conclusion. Circ_0044520 silencing plays antiproliferation and pro-apoptosis roles in LSCC cells by regulating the miR-338-3p/ROR2 axis, suggesting that the circ_0044520/miR-338-3p/ROR2 axis may be a potential regulatory mechanism for the treatment of LSCC