Circ_DLEU2 knockdown represses cell proliferation, migration and invasion, and induces cell apoptosis through the miR-582-5p/COX2 pathway in acute myeloid leukemia.

Abstract

Acute myeloid leukemia (AML) is a malignant hematological neoplasm in adults. Researche indicates that circular RNAs (circRNAs) play paramount roles in the pathological process of AML. In this study, the role of circ_DLEU2 (circ_0000488) in AML is revealed. The expression of circ_DLEU2, microRNA-582-5p (miR-582-5p) and cyclooxygenase 2 (COX2) was determined by quantitative real-time PCR. Protein expression was detected by western blot. Cell proliferation was investigated by cell cycle, 5-Ethynyl-29-deoxyuridine and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays. Cell apoptosis was elucidated by apoptosis analysis assay. The targeting relationship between miR-582-5p and circ_DLEU2 or COX2 was predicted by the starbase online database, and identified by a dual-luciferase reporter assay. Circ_DLEU2 and COX2 expression were substantially up-regulated, while miR-582-5p was down-regulated in AML marrow samples and cells compared with control groups. Circ_DLEU2 knockdown suppressed cell proliferation, whereas it induced cell arrest at G0/G1 phase and cell apoptosis in AML; however, these effects were attenuated by miR-582-5p inhibitor. Additionally, circ_DLEU2 was associated with miR-582-5p, and miR-582-5p bound to COX2 in AML cells. Also, we found that circ_DLEU2 regulated COX2 expression by interacting with miR-582-5p. Circ_DLEU2 silencing hindered AML malignant progression via downregulating COX2 through sponging miR-582-5p. Our finding provides a theoretical basis for studying circRNA-directed therapy of AML.