Decreased microRNA-30a levels are associated with enhanced ABL1 and BCR-ABL1 expression in chronic myeloid leukemia

Leuk Res. 2013 Mar;37(3):349-56. doi: 10.1016/j.leukres.2012.12.003. Epub 2013 Jan 1.

Abstract

Chronic myeloid leukemia (CML) is associated with overexpression of BCR-ABL1, a nonreceptor tyrosine kinase critical for malignant transformation. We investigated whether non-coding microRNAs (miRNAs) targeting BCR-ABL1 mRNA contribute to the pathogenesis of CML. Indeed, miR-30a targeted BCR-ABL1 and was underexpressed in bone marrow from CML patients. In K562 leukemia cells, overexpression of miR-30a reduced ABL1 and BCR-ABL1 protein expression, decreased proliferation, and arrested cell cycle progression between G1 and S. These findings strongly suggest that miR-30a acts as a tumor suppressor by downregulating ABL1 and BCR-ABL1 expression. Upregulation of miR-30a in hematopoietic cells may have therapeutic efficacy against CML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression Regulation, Leukemic* / drug effects
  • Genes, Tumor Suppressor / physiology
  • Genes, abl / genetics*
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • MicroRNAs / genetics*
  • RNA, Small Interfering / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • MIRN30b microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Fusion Proteins, bcr-abl