Cancer Management and Research (Oct 2020)
CircRAD18 Accelerates the Progression of Acute Myeloid Leukemia by Modulation of miR-206/PRKACB Axis
Abstract
Yanyan Wang,1 Te Guo,2 Quan Liu,2 Xianfei Xie3 1Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2German Cancer Research Center, Heidelberg 69120, Germany; 3Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaCorrespondence: Xianfei XieDepartment of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, People’s Republic of ChinaTel +86-21-64370045Email [email protected]: Circular RNAs (circRNAs) play a crucial role in tumorigenesis. However, the effects of circRNAs on acute myeloid leukemia (AML) remain largely unexplored. We explored the function of circRAD18 in AML development.Methods: QRT-PCR was performed for the levels of circRAD18, RAD18, microRNA-206 (miR-206) and protein kinase CAMP-activated catalytic subunit beta (PRKACB). Cell Counting Kit-8 (CCK-8) assay and colony formation assay were utilized for cell proliferation. Flow cytometry analysis was carried out to analyze cell apoptosis and cell cycle process. Transwell assay was manipulated for cell migration and invasion. Western blot assay was conducted for protein levels. Dual-luciferase reporter assay was adopted to verify the interaction between miR-206 and circRAD18 or PRKACB.Results: CircRAD18 level was increased in AML patients’ blood specimens and AML cell lines compared to normal controls. CircRAD18 knockdown impeded the proliferation, migration and invasion and facilitated the apoptosis and cell cycle arrest in AML cells. Moreover, circRAD18 was identified as a sponge for miR-206, and circRAD18 knockdown-mediated effect on AML cell progression was reversed by miR-206 suppression. Additionally, PRKACB was the target gene of miR-206. MiR-206 overexpression suppressed the malignant behaviors of AML cells, while PRKACB elevation restored the effects.Conclusion: CircRAD18 aggravated the malignancy of AML cells through reducing miR-206 expression and elevating PRKACB expression, indicating circRAD18 might be a therapeutic target for AML.Keywords: AML, circRAD18, miR-206, PRKACB
