title: [DNA methylation-mediated epigenetic silencing of miR-720 contributes to leukemogenesis in acute myeloid leukemia].
abstract: OBJECTIVE
  To investigate the expression level and regulation mechanism of miR-720 as well as the association of miR-720 expression with leukemia biological characteristics.
  
  
  METHODS
  Expression and promoter methylation of miR-720 were determined by quantitive PCR and pyrosequencing in 38 patients with AML and 20 normal controls. Lentivirous-mediated miR-702 overexpression was constructed in AML cell line kasumi-1. The cell proliferation, apoptosis, cycle, colony formation, migration and P53-mediated apoptosis pathway were determined.
  
  
  RESULTS
  AML patients showed significantly lower miR-720 expression compared with normal controls (0.69±0.09 vs 3.00±0.46, P<0.01); The methylation level of miR-720 promoter region in AML patients were significantly higher than normal controls [(75.56±2.35)% vs (47.65±2.78)%, P<0.01]. miR-720 overexpression in kasumi-1 cells induced significantly increased cell apoptosis (P=0.017), elevated apoptosis sensitivity to etoposide (P=0.004), and reduced cell proliferation (P<0.01). miR-720 overexpression also induced reduced colony formation (P=0.005), cell cycle arrest in G(1)/G(0) phase and decreased migration ability in kasumi-1 cells. In addition, overexpression of miR-720 significantly induced increased cell apoptosis-related proteins including P53 and Bax, and activation of NF-κB signal transduction pathway. After kasumi-1 cells were treated with 1uM decitabine for 48 hours, miR-720 promoter methylation reduced significantly, and miR-720 expression significantly increased.
  
  
  CONCLUSIONS
  The expression of miR-720 in AML patients reduced significantly, and DNA methylation-mediated epigenetic silencing of miR-720 contributed to maintain the malignant characteristics of AML.
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Shanhao
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Pei
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Kongfei
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Peisheng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: DU
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Keya
authors.initials: K
authors.lastname: Sha
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Hematology,Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo　315040, China.
authors.forename: Shuangyue
authors.initials: S
authors.lastname: Li
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D035683:MicroRNAs