Altered expression of miR-24, miR-126 and miR-365 does not affect viability of childhood TCF3-rearranged leukemia cells

Leukemia. 2014 May;28(5):1008-14. doi: 10.1038/leu.2013.308. Epub 2013 Oct 23.

Abstract

Among the microRNAs (miRNAs) that control different cellular processes, miR-24, miR-126 and miR-365 were shown to regulate cell cycle progression and apoptosis in various types of tumors. Interestingly, these three miRNAs were downregulated in pediatric TCF3-rearranged B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we showed that individual or combined overexpression of miR-24, miR-126 and miR-365 can neither alter the cell cycle progression nor the amount of apoptosis in 697, KASUMI-2 or MHH-CALL-3 TCF3-rearranged leukemic cells. We further integrated the miRNA-mRNA expression data of 37 children with BCP-ALL to identify candidate target genes for these three miRNAs. However, the expression levels of selected candidate target genes (ELL, EBF3 and IRF4 for miR-24, PITPNC1 for miR-126 and ZAP-70 for miR-365) did not reduce upon miRNAs overexpression in MHH-CALL-3 TCF3-rearranged leukemic cells. Although the expression level of AURKB-a validated target for miR-24-was reduced upon miR-24 overexpression in hepatocarcinoma HEP-G2 cells, overexpression of miR-24 cannot alter AURKB expression levels in MHH-CALL-3 TCF3-rearranged leukemic cells. Taken together, our data suggest that miRNAs' function is highly tissue-dependent and that a defined biological target gene or function of one miRNA in a specific tissue cannot be extended as a generalized target/function for that miRNA in all types of cells/tissues.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Apoptosis
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • DNA Primers
  • Gene Rearrangement*
  • Humans
  • MicroRNAs / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Real-Time Polymerase Chain Reaction

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA Primers
  • MicroRNAs
  • TCF3 protein, human