The tumor suppressive role of miRNA-370 by targeting FoxM1 in acute myeloid leukemia.
The tumor suppressive role of miRNA-370 by targeting FoxM1 in acute myeloid leukemia.
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miRNA-370靶向FoxM1对急性髓系白血病的抑癌作用
DOI：
10.1186/1476-4598-11-56
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发表时间：
2012-08-17
期刊：
影响因子：
37.3
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Zhang X;Zeng J;Zhou M;Li B;Zhang Y;Huang T;Wang L;Jia J;Chen C
方法检测48例初治急性髓细胞白血病（AML）患者、40例首次完全缓解（CR）的AML患者和21例健康对照者的miR-370和FoxM 1的表达水平。采用实时荧光定量PCR、Western blot、集落形成实验和β-半乳糖苷酶（SA-β-Gal）染色等方法，观察miR-370和FoxM 1过表达或抑制对白血病细胞系和原代白血病细胞的影响。在48例AML患者的白血病样本中，有37例的miR-370表达水平低于来自健康成人个体的骨髓细胞。miR-370在HL 60和K562细胞中的异位表达导致细胞生长停滞和衰老。相反，使用RNA干扰消除miR-370表达增强了这些白血病细胞的增殖。从机制上讲，miR-370靶向转录因子FoxM 1，这是一种公认的促进细胞周期进程的致癌因子。此外，当用DNA甲基化抑制剂5-aza-2′-deoxycytidine处理HL 60和K562细胞时，miR-370表达上调，这表明miR-370在白血病细胞中存在表观遗传沉默。因此，miR-370的表观遗传学沉默导致FoxM 1表达的去抑制，从而有助于AML的发生和进展。
BackgroundRecent evidence has accumulated that MicroRNA (miRNA) dysregulation occurs in the majority of human malignancies including acute myeloid leukemia (AML) and may contribute to onco-/leukemo-genesis.MethodsThe expression levels of miR-370 and FoxM1 were assessed in 48 newly diagnosed AML patients, 40 AML patients in 1stcomplete remission (CR) and 21 healthy controls. Quantitative real-time PCR, western blots, colony formation assay, and β-Galactosidase ( SA-β-Gal) staining were used to characterize the changes induced by overexpression or inhibition of miR-370 or FoxM1.ResultsWe found that the down-regulation of miR-370 expression was a frequent event in both leukemia cell lines and primary leukemic cells from patients with de novo AML. Lower levels of miR-370 expression were found in 37 of 48 leukemic samples from AML patients compared to those in bone marrow cells derived from healthy adult individuals. Ectopic expression of miR-370 in HL60 and K562 cells led to cell growth arrest and senescence. In contrast, depletion of miR-370 expression using RNA interference enhanced the proliferation of those leukemic cells. Mechanistically, miR-370 targets the transcription factor FoxM1, a well established oncogenic factor promoting cell cycle progression. Moreover, when HL60 and K562 cells were treated with 5-aza-2′-deoxycytidine, a DNA methylation inhibitor, miR-370 expression was up-regulated, which indicates epigenetic silencing of miR-370 in leukemic cells.ConclusionsTaken together, miR-370 may function as a tumor suppressor by targeting FoxM1, and the epigenetic silence of miR-370 thus leads to derepression of FoxM1 expression and consequently contributes to AML development and progression.
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DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
11.5
作者：
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通讯作者：
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影响因子：
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作者：
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Margalit H
影响因子：
9.8
作者：
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS
通讯作者：
Marks DS
影响因子：
37.3
作者：
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通讯作者：
García-Foncillas J