Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663

J Hematol Oncol. 2011 Apr 25:4:20. doi: 10.1186/1756-8722-4-20.

Abstract

Background: Differentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized.

Methods: Using bioinformatics and in vitro experiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation.

Results: Six microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV) backbone incorporating the spleen focus forming virus (SFFV-F) promoter to drive miR-663 expression, as the CMV (Cytomegalovirus) promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiation in vitro.

Conclusions: Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic / drug effects*
  • HL-60 Cells
  • Humans
  • Lentivirus / genetics
  • MicroRNAs / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen Focus-Forming Viruses / genetics
  • Time Factors
  • Transfection
  • Tretinoin / pharmacology*
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents
  • MIRN663 microRNA, human
  • MicroRNAs
  • Tretinoin