Wei Chang1, Zhen Shang2, Xi Ming2, Jiaying Wu2, Yi Xiao3. 1. Department of Hematology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan City, Hubei Province, China. 2. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, China. 3. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, China. yixiao@tjh.tjmu.edu.cn.
Abstract
BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. Circular RNAs (circRNAs) play crucial roles in AML progression. This study aimed to explore the function and potential mechanism of circRNA Scm like with four mbt domains 2 (circ-SFMBT2; hsa_circ_0017639) in AML. METHODS: The levels of circ-SFMBT2, microRNA-582-3p (miR-582-3p) and zinc finger and BTB domain containing 20 (ZBTB20) were measured by quantitative real-time PCR and Western blot. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and transwell assays were used to evaluate cell proliferation, apoptosis, migration and invasion. Glycolysis was assessed by detecting glucose consumption, lactate production and ATP/ADP ratios. The related protein expression was examined by Western blot. The binding relationship between miR-582-3p and circ-SFMBT2/ZBTB20 was verified by dual-luciferase reporter assay. RESULTS: Circ-SFMBT2 and ZBTB20 levels were elevated, while miR-582-3p level was reduced in AML patients and cells. Depletion of circ-SFMBT2/ZBTB20 impeded proliferation, migration, invasion and glycolysis and induced apoptosis in AML cells. Moreover, circ-SFMBT2 facilitated AML progression by sponging miR-582-3p, and miR-582-3p targeted ZBTB20 to hinder AML development. CONCLUSION: Knockdown of circ-SFMBT2 suppressed AML progression by regulating the miR-582-3p/ZBTB20 axis, which might provide a potential therapeutic strategy for AML.
BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. Circular RNAs (circRNAs) play crucial roles in AML progression. This study aimed to explore the function and potential mechanism of circRNA Scm like with four mbt domains 2 (circ-SFMBT2; hsa_circ_0017639) in AML. METHODS: The levels of circ-SFMBT2, microRNA-582-3p (miR-582-3p) and zinc finger and BTB domain containing 20 (ZBTB20) were measured by quantitative real-time PCR and Western blot. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and transwell assays were used to evaluate cell proliferation, apoptosis, migration and invasion. Glycolysis was assessed by detecting glucose consumption, lactate production and ATP/ADP ratios. The related protein expression was examined by Western blot. The binding relationship between miR-582-3p and circ-SFMBT2/ZBTB20 was verified by dual-luciferase reporter assay. RESULTS: Circ-SFMBT2 and ZBTB20 levels were elevated, while miR-582-3p level was reduced in AML patients and cells. Depletion of circ-SFMBT2/ZBTB20 impeded proliferation, migration, invasion and glycolysis and induced apoptosis in AML cells. Moreover, circ-SFMBT2 facilitated AML progression by sponging miR-582-3p, and miR-582-3p targeted ZBTB20 to hinder AML development. CONCLUSION: Knockdown of circ-SFMBT2 suppressed AML progression by regulating the miR-582-3p/ZBTB20 axis, which might provide a potential therapeutic strategy for AML.
Authors: Asim Khwaja; Magnus Bjorkholm; Rosemary E Gale; Ross L Levine; Craig T Jordan; Gerhard Ehninger; Clara D Bloomfield; Eli Estey; Alan Burnett; Jan J Cornelissen; David A Scheinberg; Didier Bouscary; David C Linch Journal: Nat Rev Dis Primers Date: 2016-03-10 Impact factor: 52.329