A new molecular network comprising PU.1, interferon regulatory factor proteins and miR-342 stimulates ATRA-mediated granulocytic differentiation of acute promyelocytic leukemia cells.
In the acute promyelocytic leukemia (APL) bearing the t(15;17), all-trans-retinoic acid (ATRA) treatment induces granulocytic maturation and complete remission of leukemia. We identified miR-342 as one of the microRNAs (miRNAs) upregulated by ATRA during APL differentiation. This miRNA emerged as a direct transcriptional target of the critical hematopoietic transcription factors PU.1 and interferon regulatory factor (IRF)-1 and IRF-9. IRF-1 maintains miR-342 at low levels, whereas the binding of PU.1 and IRF-9 in the promoter region following retinoic ATRA-mediated differentiation, upregulates miR-342 expression. Moreover, we showed that enforced expression of miR-342 in APL cells stimulated ATRA-induced differentiation. These data identified miR-342 as a new player in the granulocytic differentiation program activated by ATRA in APL.
De Marchis
M L
ML
Department of Genetics and Molecular Biology, Institute Pasteur Cenci-Bolognetti, Sapienza University, Rome, Italy.
Ballarino
M
M
Salvatori
B
B
Puzzolo
M C
MC
Bozzoni
I
I
Fatica
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016130:Immunophenotyping; D050856:Interferon Regulatory Factor-1 / Q000235:genetics* / Q000378:metabolism; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000235:genetics* / Q000378:metabolism; D007438:Introns / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000099232:Proto-Oncogene Protein Spi-1
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D050856:Interferon Regulatory Factor-1; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014212:Tretinoin; D000099232:Proto-Oncogene Protein Spi-1; C484449:EVL protein, human; C494257:IRF1 protein, human; C494227:IRF9 protein, human