title: MiR-370 sensitizes chronic myeloid leukemia K562 cells to homoharringtonine by targeting Forkhead box M1.
abstract: BACKGROUND
  Homoharringtonine (HHT) is a kind of cephalotaxus alkaloid used in traditional Chinese medicine. Although HHT has been successfully used as a therapeutic agent for leukemia, the drug resistance and toxicity are major concerns. MicroRNAs (miRNAs) have been identified to modulate cellular sensitivity to anticancer drugs. We examined the synergistic action between miR-370 and HHT in vitro and in vivo.
  
  
  METHODS
  The synergistic action between miR-370 and HHT was examined by flow cytometry. The effect of HHT on miR-370 expression was determined by quantitative RT-PCR (qRT-PCR). The expression of miR-370 and Forkhead box M1 (FoxM1) in 23 patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) and 10 patients with blast-crisis CML (CML-BP) as well as miR-370-targeted FoxM1 was determined by qRT-PCR and western blot analysis.
  
  
  RESULTS
  Ectopic expression of miR-370 sensitized the CML K562 cell line to HHT by targeting FoxM1, the major regulator in cell proliferation and apoptosis. miR-370 significantly promoted HHT-mediated cell apoptosis and miR-370 and HHT cooperated in affecting FoxM1 expression. As well, miR-370 was moderately upregulated after HHT treatment in K562 cells. In addition, the expression of miR-370 was significantly reduced in CML patients as compared with healthy controls. Furthermore, the expression of miR-370 was lower in CML-BP than CML-CP patients.
  
  
  CONCLUSIONS
  MiR-370 sensitized K562 cells to HHT by inducing apoptosis in part by downregulation of FoxM1 expression. These findings may provide further information for CML treatment with HHT.
authors.forename: MinRan
authors.initials: M
authors.lastname: Zhou
authors.forename: JiPing
authors.initials: J
authors.lastname: Zeng
authors.forename: XiaoMing
authors.initials: X
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: HaiYu
authors.initials: H
authors.lastname: Shen
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: LiXiang
authors.initials: L
authors.lastname: Wang
authors.forename: JiHui
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University School of Medicine, Jinan, P,R, China. chency@sdu.edu.cn.
authors.forename: ChunYan
authors.initials: C
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D015536:Down-Regulation; D005434:Flow Cytometry; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000187:drug effects*; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D035683:MicroRNAs / Q000502:physiology*; D016133:Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D006248:Harringtonines; C526503:MIRN370 microRNA, human; D035683:MicroRNAs; D000077863:Homoharringtonine