title: MicroRNA-125b inhibits AML cells differentiation by directly targeting Fes.
abstract: MicroRNA-125b (miR-125b) has been reported to be upregulated in several kinds of leukemia, suggesting that miR-125b plays a role in Leukemia development. In this study, it was shown that miR-125b expression level decreased in response to 1α, 25-dihydroxy-vitamin D3 (1,25D3) in a dose- and time-dependent manner and miR-125b blocked 1,25D3-induced monocytic differentiation of U937 cells. In addition, miR-125b decreased mRNA expression of myelomonocytic differentiation markers, including CD11c, CD18 and CD64 and arrested the cell cycle at the S phase in U937 and HL60 cells. Fes was identified as a novel direct target of miR-125b and miR-125b could also reduce the expression levels of PU.1 and macrophage colony-stimulating factor receptor (MCSFR). Furthermore, Fes was found to be involved in monocytic differentiation via upregulation of PU.1 and MCSFR and Fes siRNA could also inhibit 1,25D3-induced monocytic differentiation of U937 and HL60 cells and decrease mRNA expression of CD11c, CD18 and CD64. Importantly, the inhibition of Fes siRNA on 1,25D3-induced monocytic differentiation could be rescued by transfection with miR-125b inhibitor. Our data highlights an important role of miR-125b in AML progression, implying the potential application of miR-125b in AML therapy.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Jinhang
authors.initials: J
authors.lastname: Hu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Zheng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Shen
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China; Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Electronic address: zhlf@cpu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Xi
mesh_terms: D020413:3' Untranslated Regions; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051578:Proto-Oncogene Proteins c-fes / Q000235:genetics* / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D016186:Receptor, Macrophage Colony-Stimulating Factor; C496645:FES protein, human; D051578:Proto-Oncogene Proteins c-fes; D002117:Calcitriol
keywords: AML; Fes; MCSFR; Monocytic differentiation; PU.1; microRNA-125b