MiR-370 sensitizes chronic myeloid leukemia K562 cells to homoharringtonine by targeting Forkhead box M1

Journal of Translational Medicine

ChunYan Chen¹  JiHui Jia⁵  LiXiang Wang²  Yue Fu⁵  HaiYu Shen³  Tao Huang⁵  Qing Guo⁵  XiaoMing Wang⁵  JiPing Zeng⁴  MinRan Zhou¹ 

[1] Department of Hematology, Qilu Hospital, Shandong University School of Medicine, Jinan, P.R. China;Department of Pharmacology, Shandong University School of Medicine, Jinan, P.R. China;Department of Gastrointestinal Surgery, Jinan Central Hospital, Shandong University School of Medicine, Jinan, P.R. China;Department of Biochemistry, Shandong University School of Medicine, Jinan, P.R. China;Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, Shandong University School of Medicine, Jinan, P.R. China

关键词: Chronic myeloid leukemia;    Cellular apoptosis;    HHT;    miR-370;   

Others  :  824968
DOI  :  10.1186/1479-5876-11-265

 received in 2013-06-28, accepted in 2013-10-11,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Zhou et al.; licensee BioMed Central Ltd.

【 图 表 】

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