Inhibition of the Pim1 oncogene results in diminished visual function

PLoS One. 2012;7(12):e52177. doi: 10.1371/journal.pone.0052177. Epub 2012 Dec 26.

Abstract

Our objective was to profile genetic pathways whose differential expression correlates with maturation of visual function in zebrafish. Bioinformatic analysis of transcriptomic data revealed Jak-Stat signalling as the pathway most enriched in the eye, as visual function develops. Real-time PCR, western blotting, immunohistochemistry and in situ hybridization data confirm that multiple Jak-Stat pathway genes are up-regulated in the zebrafish eye between 3-5 days post-fertilisation, times associated with significant maturation of vision. One of the most up-regulated Jak-Stat genes is the proto-oncogene Pim1 kinase, previously associated with haematological malignancies and cancer. Loss of function experiments using Pim1 morpholinos or Pim1 inhibitors result in significant diminishment of visual behaviour and function. In summary, we have identified that enhanced expression of Jak-Stat pathway genes correlates with maturation of visual function and that the Pim1 oncogene is required for normal visual function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Electroretinography
  • Gene Expression Regulation, Developmental*
  • Larva / drug effects
  • Larva / growth & development
  • Larva / metabolism
  • Morpholinos / pharmacology*
  • Phylogeny
  • Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-pim-1 / genetics
  • Proto-Oncogene Proteins c-pim-1 / metabolism
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Vision Disorders / drug therapy
  • Vision Disorders / etiology*
  • Vision Disorders / pathology
  • Zebrafish / genetics
  • Zebrafish / growth & development
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Morpholinos
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Zebrafish Proteins
  • socs1a protein, zebrafish
  • socs3a protein, zebrafish
  • Proto-Oncogene Proteins c-pim-1

Grant support

The authors thank the Irish Research Council for Science Engineering and Technology (IRCSET) Graduate Education Programme (GREP), and Science Foundation Ireland (SFI) SFI 04/IN3/B559 (BK), and SFI 06/RFP/BIM052 (BK) for funding support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.