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

Molecular Cancer

Research

Jiping Zeng¹  Yuanyuan Zhang²  Chunyan Chen²  Minran Zhou²  Xiaolu Zhang³  Tao Huang⁴  Lixiang Wang⁵  Jihui Jia⁵  Bingnan Li⁶ 

[1] Department of Biochemistry, Shandong University, Jinan, China;Department of Hematology, Qilu Hospital, Shandong University, No.107, Wenhua Xi Road, 250012, Jinan, Shandong, P. R. China;Department of Hematology, Qilu Hospital, Shandong University, No.107, Wenhua Xi Road, 250012, Jinan, Shandong, P. R. China;Department of Medicine, Division of Hematology and CMM, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden;Department of Hematology, Qilu Hospital, Shandong University, No.107, Wenhua Xi Road, 250012, Jinan, Shandong, P. R. China;Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, China;Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, China;Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, China;Department of Medicine, Division of Hematology and CMM, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden;

关键词: miR-370;    FoxM1;    AML;    Cellular senescence;   

DOI  :  10.1186/1476-4598-11-56

 received in 2012-04-21, accepted in 2012-08-06,  发布年份 2012

来源: Springer

【 摘 要 】

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 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.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.

【 授权许可】

Unknown   
© Zhang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.