Myeloid leukemia with high EVI1 expression is sensitive to 5-aza-2′-deoxycytidine by targeting miR-9

• F. Li ^[1] ; W. He ^[1] ; R. Geng ^[1] ; X. Xie ^[1]
  1. [1] Tongji University

     Tongji University

     China

     
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 1, 2020, págs. 137-143
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose High expression of ecotropic viral integration site 1 (EVI1) has been associated with a poor prognosis in leukemia patients, but the underlying mechanism remains unclear. Aberrant expression of microRNAs plays critical roles in leukemia development. MiR-9 is a putative potential target of EVI1. We have investigated the regulating mechanism of miR-9 by EVI1 in leukemia cells.

    Methods We first examined the relationship between miR-9 and EVI1 expression levels in nine leukemia cell lines by RT-PCR. Then we forced high expression of EVI1 in UoCM1 and K562 cells to confirm the downregulation of miR-9 by EVI1. Methylation of the miR-9 promoter region was detected by DNA bisulfite sequencing. We treated the EVI1-overexpressing cells with the hypomethylating agent 5-aza-2′-deoxycytidine (5-AZA) to reverse EVI1-induced hypermethylation of miR-9.

    Results EVI1 and miR-9 expression was negative related. Forced expression of EVI1 downregulated miR-9 by inducing hypermethylation of the miR-9 promoter. 5-AZA reversed high EVI1-induced hypermethylation of the miR-9 promoter and restored the expression of miR-9. 5-AZA induced extensive apoptosis and inhibited proliferation through cell cycle arrest in EVI1-overexpressing leukemia cells.

    Conclusions Our results suggest that EVI1 may be involved in leukemia cell proliferation and apoptosis via the regulation of miR-9 promoter methylation. 5-AZA may represent a promising therapeutic option for EVI1-high leukemia patients.