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Publication : MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1.

First Author  Rao DS Year  2010
Journal  Immunity Volume  33
Issue  1 Pages  48-59
PubMed ID  20598588 Mgi Jnum  J:162004
Mgi Id  MGI:4462291 Doi  10.1016/j.immuni.2010.06.013
Citation  Rao DS, et al. (2010) MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1. Immunity 33(1):48-59
abstractText  MicroRNAs (miRNAs) can influence lineage choice or affect critical developmental checkpoints during hematopoiesis. We examined the role of the p53-induced microRNA miR-34a in hematopoiesis by gain-of-function analysis in murine bone marrow. Constitutive expression of miR-34a led to a block in B cell development at the pro-B-cell-to-pre-B-cell transition, leading to a reduction in mature B cells. This block appeared to be mediated primarily by inhibited expression of the transcription factor Foxp1. Foxp1 was a direct target of miR-34a in a 3'-untranslated region (UTR)-dependent fashion. Knockdown of Foxp1 by siRNA recapitulated the B cell developmental phenotype induced by miR-34a, whereas cotransduction of Foxp1 lacking its 3' UTR with miR-34a rescued B cell maturation. Knockdown of miR-34a resulted in increased amounts of Foxp1 and mature B cells. These findings identify a role for miR-34a in connecting the p53 network with suppression of Foxp1, a known B cell oncogene.
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