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Updated: Jun 18, 2026

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
11:06

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

Published on: September 20, 2017

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through

A R R Forrest1, M Kanamori-Katayama, Y Tomaru

  • 1LSA Technology Development Unit, Omics Science Center, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan. alistair.forrest@gmail.com

Leukemia
|December 4, 2009
PubMed

Insights

This study reveals that specific microRNAs can overcome differentiation blocks in acute myeloid leukemia (AML) cells. Combinations of these microRNAs induce cell-cycle arrest and apoptosis, offering new therapeutic avenues for AML.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • Acute myeloid leukemia (AML) is characterized by blocked myeloid differentiation and uncontrolled progenitor proliferation.
  • THP-1 cells, an M5-AML model with MLL-MLLT3 fusion, can be induced to differentiate into monocytes using phorbol myristate acetate (PMA).

Purpose of the Study:

  • To identify microRNAs regulated by PMA in THP-1 cells.
  • To investigate the role of specific microRNAs in AML cell differentiation and cell-cycle regulation.
  • To elucidate the combinatorial effects of microRNAs in cellular systems.

Main Methods:

  • Microarray analysis to identify PMA-regulated microRNAs in THP-1 cells.
  • Overexpression of identified microRNAs to assess their effects on cell differentiation and cell-cycle arrest.
  • Analysis of microRNA precursor processing and targeting of cell-cycle regulators.

Main Results:

  • Twenty-three microRNAs were found to be regulated by PMA.
  • Four microRNAs (miR-155, miR-222, miR-424, miR-503) were identified as pro-differentiative, inducing cell-cycle arrest and partial differentiation.
  • miR-155 and miR-222 induced G2 arrest and apoptosis, respectively.
  • miR-424 and miR-503, derived from a repressed polycistronic precursor, target cell-cycle regulators, induce G1 arrest, and downregulate miR-9.

Conclusions:

  • Specific microRNAs can overcome differentiation blocks in AML.
  • Combinatorial action of microRNAs leads to enhanced cellular effects, including cell-cycle arrest and apoptosis.
  • The MLL-MLLT3 fusion represses miR-424-503, highlighting a mechanism in leukemogenesis.

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