[DNA methylation-mediated epigenetic silencing of miR-720 contributes to leukemogenesis in acute myeloid leukemia]

Zhonghua Xue Ye Xue Za Zhi. 2014 Nov;35(11):1009-12. doi: 10.3760/cma.j.issn.0253-2727.2014.11.013.
[Article in Chinese]


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.

Conclusion: 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.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • MicroRNAs / genetics*
  • Promoter Regions, Genetic


  • MicroRNAs