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

Publication ,  Journal Article
Lu, Y; Thomson, JM; Wong, HYF; Hammond, SM; Hogan, BLM
Published in: Dev Biol
October 15, 2007

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.

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Published In

Dev Biol

DOI

ISSN

0012-1606

Publication Date

October 15, 2007

Volume

310

Issue

2

Start / End Page

442 / 453

Location

United States

Related Subject Headings

  • Stem Cells
  • Pulmonary Surfactant-Associated Protein C
  • Promoter Regions, Genetic
  • Peptides
  • MicroRNAs
  • Mice, Transgenic
  • Mice
  • Lung
  • Intercellular Signaling Peptides and Proteins
  • Epithelial Cells
 

Citation

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Lu, Y., Thomson, J. M., Wong, H. Y. F., Hammond, S. M., & Hogan, B. L. M. (2007). Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol, 310(2), 442–453. https://doi.org/10.1016/j.ydbio.2007.08.007
Lu, Yun, J Michael Thomson, Ho Yuen Frank Wong, Scott M. Hammond, and Brigid L. M. Hogan. “Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells.Dev Biol 310, no. 2 (October 15, 2007): 442–53. https://doi.org/10.1016/j.ydbio.2007.08.007.
Lu, Yun, et al. “Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells.Dev Biol, vol. 310, no. 2, Oct. 2007, pp. 442–53. Pubmed, doi:10.1016/j.ydbio.2007.08.007.
Journal cover image

Published In

Dev Biol

DOI

ISSN

0012-1606

Publication Date

October 15, 2007

Volume

310

Issue

2

Start / End Page

442 / 453

Location

United States

Related Subject Headings

  • Stem Cells
  • Pulmonary Surfactant-Associated Protein C
  • Promoter Regions, Genetic
  • Peptides
  • MicroRNAs
  • Mice, Transgenic
  • Mice
  • Lung
  • Intercellular Signaling Peptides and Proteins
  • Epithelial Cells