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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Pelosi A,Careccia S,Lulli V,Romania P,Marziali G,Testa U,Lavorgna S,Lo-Coco F,Petti MC,Calabretta B,Levrero M,Piaggio G,Rizzo MGdoi
10.1038/onc.2012.398subject
Has Abstractpub_date
2013-08-01 00:00:00pages
3648-54issue
31eissn
0950-9232issn
1476-5594pii
onc2012398journal_volume
32pub_type
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