siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth

  • Authors:
    • Ailyn Choo
    • Patricia Palladinetti
    • Tiffany Holmes
    • Shreerupa Basu
    • Sylvie Shen
    • Richard B. Lock
    • Tracey A. O'Brien
    • Geoff Symonds
    • Alla Dolnikov
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.175
  • Pages: 175-183
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Abstract

Interferon regulatory factor (IRF) 1 and its functional antagonist IRF2 were originally discovered as transcription factors that regulate the interferon-β gene. Control of cell growth has led to the definition of IRF1 as a tumour suppressor gene and IRF2 as an oncogene. Clinically, approximately 70% of cases of acute myeloid leukaemia demonstrate dysregulated expression of IRF1 and/or IRF2. Our previous studies have shown that human leukaemic TF-1 cells exhibit abnormally high expression of both IRF1 and IRF2, the latter acting to abrogate IRF1 tumour suppression, making these cells ideal for analysis of down-regulation of IRF2 expression. A novel G418 screening protocol was developed and used for identifying effective siRNA that targets IRF2 (siIRF2). Using optimized siIRF2 in leukaemic TF-1 cells, IRF2 was down-regulated by approximately 70% at both mRNA and protein levels. Phenotypically, this resulted in growth inhibition associated with G2/M arrest as well as induction of polyploidy, differentiation and apoptosis. In contrast to these results, siIRF2 targeting did not affect normal haematopoietic stem/progenitor cell growth. These results indicate the potential utility of IRF2 inhibition as a therapeutic approach to cancer.

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July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Choo A, Palladinetti P, Holmes T, Basu S, Shen S, Lock RB, O'Brien TA, Symonds G and Dolnikov A: siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth. Int J Oncol 33: 175-183, 2008.
APA
Choo, A., Palladinetti, P., Holmes, T., Basu, S., Shen, S., Lock, R.B. ... Dolnikov, A. (2008). siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth. International Journal of Oncology, 33, 175-183. https://doi.org/10.3892/ijo.33.1.175
MLA
Choo, A., Palladinetti, P., Holmes, T., Basu, S., Shen, S., Lock, R. B., O'Brien, T. A., Symonds, G., Dolnikov, A."siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth". International Journal of Oncology 33.1 (2008): 175-183.
Chicago
Choo, A., Palladinetti, P., Holmes, T., Basu, S., Shen, S., Lock, R. B., O'Brien, T. A., Symonds, G., Dolnikov, A."siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth". International Journal of Oncology 33, no. 1 (2008): 175-183. https://doi.org/10.3892/ijo.33.1.175