Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3′UTR element in CSF-1R mRNA

Ho Hyung Woo, Sang C. Lee, Jha'nae B. Stoffer, Demaretta Rush, Setsuko K Chambers

Research output: Contribution to journalArticle

Abstract

Vigilin, a nucleocytoplasmic shuttling protein, post-transcriptionally suppresses proto-oncogene c-fms expression (encoding CSF-1R) in breast cancer by binding to a 69 nt cis-acting 3-UTR element in CSF-1R mRNA. CSF-1R is an important mediator of breast cancer development, metastasis, and survival. We confirm that vigilin decreases in vitro reporter luciferase activity as well as the translation rate of target mRNAs. We further explore the mechanism of suppression of CSF-1R. We show that the 69 nt binding element has profound effects on translation efficiency of CSF-1R mRNA, not seen in the presence of mutation of the element. Also, mutation of the 69 nt element in the CSF-1R mRNA 3′UTR both interferes with direct vigilin binding and obviates effect of vigilin overexpression on translational repression of CSF-1R. We show that stable vigilin binding requires the full length 69 nt CSF-1R element, including the 26 nt pyrimidine-rich core. Furthermore, titration of endogenous vigilin and other proteins which bind the 69 nt element, by exogenously introduced CSF-1R mRNA 3′UTR containing the pyrimidine-rich sequence, increases the adhesion, motility, and invasion of breast cancer cells. This phenotypic effect is not seen when the 69 nt element is deleted. Lastly, we are the first to show that human breast tissues exhibit strong vigilin expression in normal breast epithelium. Our pilot data suggest decreased vigilin protein expression, along with shift from the nucleus to the cytoplasmic location, in the transition to ductal carcinoma in situ.

LanguageEnglish (US)
Pages106-115
Number of pages10
JournalTranslational Oncology
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2019

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3' Untranslated Regions
Breast Neoplasms
Phenotype
Messenger RNA
fms Genes
Breast
Mutation
Proteins
Carcinoma, Intraductal, Noninfiltrating
high density lipoprotein binding protein
Luciferases
Epithelium
Neoplasm Metastasis
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3′UTR element in CSF-1R mRNA. / Woo, Ho Hyung; Lee, Sang C.; Stoffer, Jha'nae B.; Rush, Demaretta; Chambers, Setsuko K.

In: Translational Oncology, Vol. 12, No. 1, 01.01.2019, p. 106-115.

Research output: Contribution to journalArticle

Woo, Ho Hyung ; Lee, Sang C. ; Stoffer, Jha'nae B. ; Rush, Demaretta ; Chambers, Setsuko K. / Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3′UTR element in CSF-1R mRNA. In: Translational Oncology. 2019 ; Vol. 12, No. 1. pp. 106-115.
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