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The tumor suppressive role of miRNA-370 by targeting FoxM1 in acute myeloid leukemia.


ABSTRACT:

Background

Recent 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.

Methods

The expression levels of miR-370 and FoxM1 were assessed in 48 newly diagnosed AML patients, 40 AML patients in 1st complete remission (CR) and 21 healthy controls. Quantitative real-time PCR, western blots, colony formation assay, and ?-Galactosidase ( SA-?-Gal) staining were used to characterize the changes induced by overexpression or inhibition of miR-370 or FoxM1.

Results

We 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.

Conclusions

Taken 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.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC3533721 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Publications

The tumor suppressive role of miRNA-370 by targeting FoxM1 in acute myeloid leukemia.

Zhang Xiaolu X   Zeng Jiping J   Zhou Minran M   Li Bingnan B   Zhang Yuanyuan Y   Huang Tao T   Wang Lixiang L   Jia Jihui J   Chen Chunyan C  

Molecular cancer 20120817


<h4>Background</h4>Recent 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.<h4>Methods</h4>The expression levels of miR-370 and FoxM1 were assessed in 48 newly diagnosed AML patients, 40 AML patients in 1st complete remission (CR) and 21 healthy controls. Quantitative real-time PCR, western blots, colony formation assay, and β-Galactosidase ( SA-β-Gal) stain  ...[more]

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