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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lu, Y; Thomson, JM; Wong, HYF; Hammond, SM; Hogan, BLM

Published Date

  • October 2007

Published In

Volume / Issue

  • 310 / 2

Start / End Page

  • 442 - 453

PubMed ID

  • 17765889

Pubmed Central ID

  • 17765889

Electronic International Standard Serial Number (EISSN)

  • 1095-564X

International Standard Serial Number (ISSN)

  • 0012-1606

Digital Object Identifier (DOI)

  • 10.1016/j.ydbio.2007.08.007

Language

  • eng