Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells

Dev Biol. 2007 Oct 15;310(2):442-53. doi: 10.1016/j.ydbio.2007.08.007. Epub 2007 Aug 9.


The miR-17-92 locus encodes a cluster of 7 microRNAs transcribed as a single primary transcript. It can accelerate c-Myc induced B cell lymphoma development and is highly expressed in many tumors, including lung tumors. However, the role of miR-17-92 in development has not been well studied. From analysis of microRNAs during lung development, expression of the miR-17-92 cluster is high at early stages, but declines as development proceeds. We used the mouse surfactant protein C (Sftpc) promoter to over-express the cluster in embryonic lung epithelium. Transgenic lungs have a very abnormal lethal phenotype. They contain numerous proliferative epithelial cells that retain high levels of Sox9, a marker of distal progenitors. The differentiation of proximal epithelial cells was also inhibited. Furthermore, a significant increase in the number of neuroendocrine cell clusters was observed in the lungs of dead transgenic pups. We identify a tumor suppressor, Rbl2 which belongs to the Rb family, as a new target for miR-17-5p. Together, these studies suggest that mir-17-92 normally promotes the high proliferation and undifferentiated phenotype of lung epithelial progenitor cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Proliferation*
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Lung / cytology*
  • Lung / embryology
  • Lung / metabolism
  • Mice
  • Mice, Transgenic
  • MicroRNAs / biosynthesis*
  • Peptides / genetics
  • Peptides / metabolism
  • Promoter Regions, Genetic
  • Pulmonary Surfactant-Associated Protein C
  • Stem Cells / cytology*
  • Stem Cells / metabolism


  • Intercellular Signaling Peptides and Proteins
  • MicroRNAs
  • Peptides
  • Pulmonary Surfactant-Associated Protein C
  • Sftpc protein, mouse