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. 2022 Jun;37(6):513-526.
doi: 10.14670/HH-18-420. Epub 2022 Jan 17.

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

Huijun Yang  1 , Gang Yu  2 , Yan Wang  2 , Xing Guo  2
Affiliations

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

Huijun Yang et al. Histol Histopathol. 2022 Jun.

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 miR-338-3p. 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 anti-proliferation 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.

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