Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia

Anne Saumet, Guillaume Vetter, Manuella Bouttier, Elodie Portales-Casamar, Wyeth W. Wasserman, Thomas Maurin, Bernard Mari, Pascal Barbry, Laurent Vallar, Evelyne Friederich, Khalil Arar, Bruno Cassinat, Christine Chomienne, Charles Henri Lecellier*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    91 Citations (Scopus)

    Abstract

    Micro(mi)RNAs are small noncoding RNAs that orchestrate many key aspects of cell physiology and their deregulation is often linked to distinct diseases including cancer. Here, we studied the contribution of miRNAs in a well-characterized human myeloid leukemia, acute promyelocytic leukemia (APL), targeted by retinoic acid and trioxide arsenic therapy. We identified several miRNAs transcription- ally repressed by the APL-associated PML-RAR oncogene which are released after treatment with all-trans retinoic acid. These coregulated miRNAs were found to control, in a coordinated manner, crucial pathways linked to leukemogenesis, such as HOX proteins and cell adhesion molecules whose expressions are thereby repressed by the chemotherapy. Thus, APL appears linked to transcriptional perturbation of miRNA genes, and clinical protocols able to successfully eradicate cancer cells may do so by restoring miRNA expression. The identification of abnormal miRNA biogenesis in cancer may therefore provide novel biomarkers and therapeutic targets in myeloid leukemias.

    Original languageEnglish
    Pages (from-to)412-421
    Number of pages10
    JournalBlood
    Volume113
    Issue number2
    DOIs
    Publication statusPublished - 8 Jan 2009

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