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FoxM1 promotes development of AML by regulating Bcl-2 expression
Authors:CHEN Jin  WANG Xiao-ming  ZHOU Min-ran  SUN Ting  CHEN Zhong-min  CHEN Chun-yan
Institution:1. Anhui Medical College, Hefei 230601, China; 2. Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China; 3. School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China
Abstract:AIM: To investigate the role of Forkhead box M1 (FoxM1) and B-cell leukemia/lymphoma-2 (Bcl-2) in the pathogenesis of acute myeloid leukemia (AML). METHODS: RT-qPCR and immunofluorescence analysis were used to determine the expression of FoxM1 at mRNA and protein levels in AML-de novo patients, AML-complete remission (CR) patients, AML-refractoriness and relapse (RR) patients and healthy controls. HL60 cells and K562 cells were transfected with FoxM1 siRNA. The cell proliferation was detected by cell proliferation assay and colony formation assay on soft agar, and the cell apoptosis was determined by flow cytometry. The expression of FoxM1 and Bcl-2 at mRNA and protein levels was detected by RT-qPCR and Western blotting. The activity of bcl-2 promoter was examined by luciferase reporter assay with FoxM1 targetting. RESULTS: FoxM1 expression level in the AML-de novo patients was significantly higher than that in the healthy controls. As compared with the AML-de novo patients, FoxM1 expression in the AML-CR patients was reduced, and the FoxM1 expression level was the highest in the AML-RR patients. FoxM1 expression was inhibited in the HL60 cells and K562 cells transfected with FoxM1 siRNA. Transfection with FoxM1 siRNA in the HL60 cells and K562 cells inhibited the proliferation as compared with NC siRNA transfection, and impaired the colony formation ability. On the contrary, transfection with FoxM1 siRNA promoted the cell apoptosis. FoxM1 regulated bcl-2 expression positively. CONCLUSION: FoxM1 promotes the development of AML by regulating bcl-2 expression. Silencing of FoxM1 expression suppresses cell proliferation and promotes cell apoptosis. FoxM1 is a potential target for AML treatment.
Keywords:Acute myeloid leukemia  Forkhead box M1  Bcl-2  
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