Identification of Circular RNA Circ_0003256 as a Novel Player in Pediatric Acute Myeloid Leukemia

Abstract

Aberrant expression of circular RNAs (circRNAs) is tightly associated with the pathogenesis of human cancers, including pediatric acute myeloid leukemia (AML). In this report, we sought to define the precise action of circ_0003256 in the pathogenesis of pediatric AML. Circ_0003256, microRNA (miR)-582-3p, and protein kinase cAMP-activated catalytic subunit beta (PRKACB) were quantified by quantitative real-time polymerase chain reaction and Western blot. Cell proliferation, cycle distribution, and apoptosis were estimated by MTT, 5-ethynyl-2'-deoxyuridine, and flow cytometry assays, respectively. Direct relationships among circ_0003256, miR-582-3p, and PRKACB were verified by a dual-luciferase reporter and RNA pull-down assays. Our data indicated that circ_0003256 was highly expressed in pediatric AML patients and cells. Suppression of circ_0003256 hindered cell proliferation and promoted apoptosis in THP-1 and MV4-11 cells. Mechanistically, circ_0003256 contained functional binding sites for miR-582-3p, and circ_0003256 suppression influenced cell behaviors by upregulating miR-582-3p. MiR-582-3p directly targeted and inhibited PRKACB and the inhibition of PRKACB phenocopied miR-582-3p overexpression in regulating cell functional behaviors. Moreover, circ_0003256 involved the posttranscriptional regulation of PRKACB through miR-582-3p. Our findings identify that suppression of circ_0003256 impedes the malignant behaviors of pediatric AML cells by regulating PRKACB expression by competing for shared miR-582-3p.