MiR-370 sensitizes chronic myeloid leukemia K562 cells to homoharringtonine by targeting Forkhead box M1
MiR-370 sensitizes chronic myeloid leukemia K562 cells to homoharringtonine by targeting Forkhead box M1
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MiR-370 通过靶向 Forkhead box M1 使慢性粒细胞白血病 K562 细胞对高三尖杉酯碱敏感
DOI：
10.1186/1479-5876-11-265
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发表时间：
2013-10
影响因子：
7.4
通讯作者：
ChunYan Chen
中科院分区：
文献类型：
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作者：
Yue Fu;LiXiang Wang;JiHui Jia;ChunYan Chen
高三尖杉酯碱（Homoharringtonine，HHT）是一种三尖杉属植物的生物碱。虽然HHT已成功地用作白血病的治疗剂，但耐药性和毒性是主要问题。已经鉴定出微小RNA（miRNAs）调节细胞对抗癌药物的敏感性。方法采用流式细胞术检测miR-370与HHT在体外和体内的协同作用。通过定量RT-PCR（qRT-PCR）测定HHT对miR-370表达的影响。采用qRT-PCR和western blot分析方法检测23例初诊慢性期慢性髓细胞白血病（CML CP）和10例急变期CML（CML BP）患者中miR-370和Forkhead box M1（FoxM 1）的表达以及miR-370靶向FoxM 1的表达。细胞增殖和凋亡的主要调节因子。miR-370显著促进HHT介导的细胞凋亡，miR-370和HHT协同影响FoxM 1的表达。同样，在K562细胞中，HHT处理后miR-370适度上调。此外，与健康对照相比，CML患者中miR-370的表达显著降低。结论miR-370通过下调FoxM 1的表达，诱导K562细胞凋亡，从而对HHT敏感。这些结果可能为HHT治疗CML提供进一步的信息。
BackgroundHomoharringtonine (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 HHTin vitroandin vivo.MethodsThe 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.ResultsEctopic 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.ConclusionsMiR-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.
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影响因子：
4
作者：
Wang, Zhiwei;Li, Yiwei;Ahmad, Aamir;Banerjee, Sanjeev;Azmi, Asfar S.;Kong, Dejuan;Wojewoda, Christine;Miele, Lucio;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
3.7
作者：
Wu Z;Sun H;Zeng W;He J;Mao X
通讯作者：
Mao X
miRNA-370靶向FoxM1对急性髓系白血病的抑癌作用
影响因子：
37.3
作者：
Zhang X;Zeng J;Zhou M;Li B;Zhang Y;Huang T;Wang L;Jia J;Chen C
通讯作者：
Chen C
影响因子：
6.1
作者：
通讯作者：
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影响因子：
5.4
作者：
通讯作者：
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