miR-17-92 promotes leukemogenesis in chronic myeloid leukemia via targeting A20 and activation of NF-κB signaling

Biochem Biophys Res Commun. 2017 Jun 10;487(4):868-874. doi: 10.1016/j.bbrc.2017.04.144. Epub 2017 Apr 28.

Abstract

miR-17-92 cluster are overexpressed in hematological malignancies including chronic myeloid leukemia (CML). However, their roles and mechanisms that regulate BCR-ABL induced leukemogenesis remain unclear. In this study, we demonstrated that genomic depletion of miR-17-92 inhibited the BCR-ABL induced leukemogenesis by using a mouse model of transplantation of BCR-ABL transduced hematopoietic stem cells. Furthermore, we identified that miR-19b targeted A20 (TNFAIP3). A20 overexpression results in inactivation of NF-κB activity including decrease of phosphorylation of P65 and IκBα, leads to induce apoptosis and inhibit proliferation and cycle in CML CD34 + cells. Thus we proved that miR-17-92 is a critical contributor to CML leukemogenesis via targeting A20 and activation of NF-κB signaling. These findings indicate that miR-17-92 will be important resources for developing novel treatment strategies of CML and better understanding long-term disease control.

Keywords: A20; Chronic myeloid leukemia; NF-κB; miR-17-92.

MeSH terms

  • Animals
  • HEK293 Cells
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • RNA, Long Noncoding
  • Signal Transduction*
  • Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism*

Substances

  • MIR17HG, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Long Noncoding
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3