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

Immunity. 2010 Jul 23;33(1):48-59. doi: 10.1016/j.immuni.2010.06.013. Epub 2010 Jul 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology
  • Cell Line
  • Cloning, Molecular
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Hematopoiesis
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • Precursor Cells, B-Lymphoid / metabolism*
  • Precursor Cells, B-Lymphoid / pathology
  • Radiation Chimera
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Tumor Suppressor Protein p53 / metabolism


  • 3' Untranslated Regions
  • FOXP1 protein, human
  • Forkhead Transcription Factors
  • MIRN34 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • Tumor Suppressor Protein p53