title: Inhibition of the miR-143/145 cluster attenuated neutrophil differentiation of APL cells.
abstract: MicroRNAs can influence hematopoietic cell lineage commitment and aberrant expression of hematopoietic miRNAs contributes to AML pathology. We found that miR-143 and miR-145 expression is significantly repressed in primary AML patient samples as compared to neutrophils of healthy donors. Further analysis revealed impaired neutrophil differentiation of APL cells upon inhibition of miR-145 expression. Lastly, we identified p73 as transcriptional regulator of miR-143/145 during neutrophil differentiation of APL cells. Our data suggest that low miR-145 levels in APL, possibly due to aberrant expression of p73 transcription factors, contribute to the differentiation block seen in this disease.
authors.affiliation: Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Batliner
authors.forename: Emanuel
authors.initials: E
authors.lastname: Buehrer
authors.forename: Martin F
authors.initials: MF
authors.lastname: Fey
authors.forename: Mario P
authors.initials: MP
authors.lastname: Tschan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D014212:Tretinoin