Posttranscriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer

Mol Cell Biol. 2011 Jan;31(1):215-25. doi: 10.1128/MCB.01031-10. Epub 2010 Oct 25.

Abstract

cis-acting elements found in 3'-untranslated regions (UTRs) are regulatory signals determining mRNA stability and translational efficiency. By binding a novel non-AU-rich 69-nucleotide (nt) c-fms 3' UTR sequence, we previously identified HuR as a promoter of c-fms proto-oncogene mRNA. We now identify the 69-nt c-fms mRNA 3' UTR sequence as a cellular vigilin target through which vigilin inhibits the expression of c-fms mRNA and protein. Altering association of either vigilin or HuR with c-fms mRNA in vivo reciprocally affected mRNA association with the other protein. Mechanistic studies show that vigilin decreased c-fms mRNA stability. Furthermore, vigilin inhibited c-fms translation. Vigilin suppresses while HuR encourages cellular motility and invasion of breast cancer cells. In summary, we identified a competition for binding the 69-nt sequence, through which vigilin and HuR exert opposing effects on c-fms expression, suggesting a role for vigilin in suppression of breast cancer progression.

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
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Base Sequence
  • Binding, Competitive
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Disease Progression
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Genes, fms*
  • Humans
  • Molecular Sequence Data
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / physiopathology
  • Protein Biosynthesis
  • Proto-Oncogene Mas
  • RNA Processing, Post-Transcriptional
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • Antigens, Surface
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • high density lipoprotein binding protein