TY - JOUR
T1 - Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia
AU - Saumet, Anne
AU - Vetter, Guillaume
AU - Bouttier, Manuella
AU - Portales-Casamar, Elodie
AU - Wasserman, Wyeth W.
AU - Maurin, Thomas
AU - Mari, Bernard
AU - Barbry, Pascal
AU - Vallar, Laurent
AU - Friederich, Evelyne
AU - Arar, Khalil
AU - Cassinat, Bruno
AU - Chomienne, Christine
AU - Lecellier, Charles Henri
PY - 2009/1/8
Y1 - 2009/1/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=58849155669&partnerID=8YFLogxK
U2 - 10.1182/blood-2008-05-158139
DO - 10.1182/blood-2008-05-158139
M3 - Article
C2 - 18941112
AN - SCOPUS:58849155669
SN - 0006-4971
VL - 113
SP - 412
EP - 421
JO - Blood
JF - Blood
IS - 2
ER -