miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia
| Autor: | Maria Concetta Petti, Andrea Pelosi, F Lo-Coco, Massimo Levrero, Bruno Calabretta, Valentina Lulli, Maria Giulia Rizzo, Ugo Testa, Giulia Piaggio, Paolo Romania, Silvia Careccia, Giovanna Marziali, S Lavorgna |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Acute promyelocytic leukemia
Cancer Research Myeloid microrna Biology acute myeloid leukemia Article hemic and lymphatic diseases Cell Line Tumor Proto-Oncogene Proteins Gene expression microRNA Genetics medicine Humans Myeloid Cells Molecular Biology neoplasms Regulation of gene expression Homeodomain Proteins pbx2 Myeloid leukemia Cell Differentiation medicine.disease Gene Expression Regulation Neoplastic Leukemia Leukemia Myeloid Acute MicroRNAs medicine.anatomical_structure Phenotype Immunology Cancer research acute myeloid leukemia microRNA PBX2 Ectopic expression Granulocytes |
| Zdroj: | Oncogene |
| Popis: | MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, are involved in many complex cellular processes. Several miRNAs are differentially expressed in hematopoietic tissues and play important roles in normal differentiation, but, when aberrantly regulated, contribute to the abnormal proliferation and differentiation of leukemic cells. Recently, we reported that a small subset of miRNAs is differentially expressed in acute promyelocytic leukemia (APL) blasts and is modulated by treatment with all-trans-retinoic acid (ATRA). In particular, PML/RARα-positive blasts from APL patients display lower levels of miRNA let-7c, a member of the let-7 family, than normal promyelocytes and its expression increases after ATRA treatment. In this study, we investigated the effects of let-7c in acute myeloid leukaemia (AML) cells. We found that ectopic expression of let-7c promotes granulocytic differentiation of AML cell lines and primary blasts. Moreover, we identified PBX2, a well-known homeodomain protein whose aberrant expression enhances HoxA9-dependent leukemogenesis, as a novel let-7c target that may contribute to the AML phenotype. Together, these studies raise the possibility that perturbation of the let-7c-PBX2 pathway may have a therapeutic value in AML. |
| Databáze: | OpenAIRE |
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