Spectrum generating groups — idea and application.pdfVIP

Zhang et al. Molecular Cancer 2012, 11:56 /content/11/1/56 RESEARCH Open Access The tumor suppressive role of miRNA-370 by targeting FoxM1 in acute myeloid leukemia 1,4† 2† 1 3,4 1 1,3 3 Xiaolu Zhang , Jiping Zeng , Minran Zhou , Bingnan Li , Yuanyuan Zhang , Tao Huang , Lixiang Wang , Jihui Jia3 and Chunyan Chen1* 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 β-Galactosidase ( SA-β-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-20-deoxycytidine,