Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 551, Issue -, Pages 78-85Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.02.058
Keywords
Circ_0005774; miR-192-5p; ULK1; AML
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Circular RNA circ_0005774 and miRNA-192-5p are found to be interrelated in acute myeloid leukemia, influencing cell proliferation and apoptosis. Disruption of this pathway can inhibit cell growth and promote cell death in AML.
Circular RNAs (circRNAs) and microRNAs (miRNAs) have been emerging as new players in acute myeloid leukemia (AML). Hsa_circ_0005774 (circ_0005774) is an upregulated circRNA in pediatric AML, while its role is uncovered. Thus, we intended to measure the function and mechanism of circ_0005774 in AML leukemogenesis. Real time-quantitative PCR revealed that circ_0005774 was highly expressed in blood of pediatric AML patients and AML cells (HL-60 and NB4), accompanied with downregulated miRNA-192-5p (miR-192-5p) which was a crucial tumor-associated and leukemia-related miRNA. Circ_0005774 was abundant in miRNA response element according to CSCD software, and miR-192-5p was identified as a target of circ_0005774, as evidenced by RNA immunoprecipitation and dual-luciferase reporter assays. Cell viability assay, flow cytometry and western blotting were performed to measure cell functions. Accordingly, blocking circ_0005774 and/or overexpressing miR-192-5p could enhance apoptosis rate of HL-60 and NB4 cells, but suppress cell viability and cell cycle entrance, accompanied with depression of proliferation markers including proliferating cell nuclear antigen (PCNA), CyclinD1 and B cell lymphoma 2 (Bcl-2). Meanwhile, depleting miR-192-5p counteracted the role of circ_0005774 knockdown in AML cells. Uncoordinated 51-like kinase 1 (ULK1) was previously demonstrated to be associated with diagnosis, prognosis and therapeutic strategy for AML, and restoring ULK1 could abrogate miR-192-5p overexpression-induced effects in HL-60 and NB4 cells. Notably, ULK1 was a downstream target of miR-192-5p and indirectly modulated by circ_0005774. In conclusion, circ_0005774 knockdown repressed cell proliferation and promoted apoptosis of AML cells partially through regulating miR-192-5p/ULK1 axis. ? 2021 Elsevier Inc. All rights reserved.
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