MicroRNA-142-3p inhibits cell proliferation in human acute lymphoblastic leukemia by targeting the MLL-AF4 oncogene

Mol Biol Rep. 2013 Dec;40(12):6811-9. doi: 10.1007/s11033-013-2798-6. Epub 2013 Sep 22.

Abstract

The mixed-lineage leukemia (MLL)-AF4 fusion protein encoded by the chromosomal translocation t(4;11) predicts a poorer prognosis in acute lymphoblastic leukemia (ALL) than in other MLL-associated leukemias. However, the detailed mechanism underlying regulation of MLL-AF4 expression remains largely unknown. In this study, we showed that microRNA (miR)-142-3p was significantly downregulated in ALL patients expressing MLL-AF4. Upregulation of miR-142-3p decreased MLL-AF4 expression in the RS4;11 leukemic cell line, which suggests that MLL-AF4 is a direct target of miR-142-3p. Ectopic expression of miR-142-3p remarkably suppressed cell proliferation and induced apoptosis in RS4;11 cells expressing the MLL-AF4 fusion protein. We also found that exogenous expression of miR-142-3p strongly reduced the expression of MLL-AF4 target genes such as homeobox A (HOXA)9, HOXA7, and HOXA10 in RS4;11 cells. Taken together, our results indicate that miR-142-3p functions as a growth suppressor in MLL-AF4(+) ALL, and its suppressive effects are mediated primarily through repression of MLL-AF4 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Oncogenes*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Promoter Regions, Genetic / genetics
  • Young Adult

Substances

  • MIRN142 microRNA, human
  • MLL-AF4 fusion protein, human
  • MicroRNAs
  • Oncogene Proteins, Fusion
  • Myeloid-Lymphoid Leukemia Protein