title: miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia.
abstract: 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 leukemia (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.
authors.affiliation: Department of Experimental Oncology, Laboratory of Molecular Oncogenesis, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pelosi
authors.forename: S
authors.initials: S
authors.lastname: Careccia
authors.forename: V
authors.initials: V
authors.lastname: Lulli
authors.forename: P
authors.initials: P
authors.lastname: Romania
authors.forename: G
authors.initials: G
authors.lastname: Marziali
authors.forename: U
authors.initials: U
authors.lastname: Testa
authors.forename: S
authors.initials: S
authors.lastname: Lavorgna
authors.forename: F
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: M C
authors.initials: MC
authors.lastname: Petti
authors.forename: B
authors.initials: B
authors.lastname: Calabretta
authors.forename: M
authors.initials: M
authors.lastname: Levrero
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: M G
authors.initials: MG
authors.lastname: Rizzo
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006098:Granulocytes / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D022423:Myeloid Cells / Q000473:pathology; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; C090465:PBX2 protein, human; D011518:Proto-Oncogene Proteins; C097899:homeobox protein HOXA9; C487931:mirnlet7 microRNA, human