MicroRNA-193b regulates c-Kit proto-oncogene and represses cell proliferation in acute myeloid leukemia

Leuk Res. 2011 Sep;35(9):1226-32. doi: 10.1016/j.leukres.2011.06.010. Epub 2011 Jul 2.

Abstract

Mutations and/or overexpression of c-Kit proto-oncogene frequently occur in subsets of acute myeloid leukemia (AML) and contribute to abnormal cell proliferation and poor outcomes. We showed that c-Kit expression was subject to post-transcriptional regulation by microRNA (miRNA)-193b. Notably, miR-193b was significantly down-regulated in the examined AML cells and its levels were inversely correlated with c-Kit levels. Restoration of miR-193b expression in AML cells resulted in distinctly reduced c-Kit expression and inhibited cell growth. These data reveal a role for miR-193b dysregulation in myeloid leukemogenesis and the therapeutic promise of regulating miR-193b expression for c-Kit-positive AML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Proliferation*
  • Cells, Cultured
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Middle Aged
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-kit / genetics*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Young Adult

Substances

  • MAS1 protein, human
  • MIRN193 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-kit