The alternative spliced 3′-UTR mediated differential secretion of macrophage colony stimulating factor in breast cancer cells

Ho Hyung Woo, Setsuko K. Chambers

Research output: Contribution to journalArticlepeer-review

Abstract

CSF-1 mRNA 3′UTR variants (var) are generated from alternative splicing. CSF-1 protein encoded by var-1 mRNA with long 3′UTR derived from exon-10 is rapidly secreted compared to the CSF-1 protein encoded by var-4 mRNA with short 3′UTR derived from exon-9. Secretion kinetics indicates that HuR, which binds the CSF-1 var-1 mRNA, but not var-4 mRNA, accelerates the secretion of CSF-1 protein. HuR overexpression increases the secretion rate of CSF-1 protein. In contrast, silencing of HuR does not have such an effect, suggesting other compensatory mechanisms. Effect of the CSF-1 mRNA variant 3′UTRs on cellular phenotype shows both CSF-1 var-1 or -4 mRNA is involved in the enhanced rates of migration and invasion observed by both in vitro in breast cancer cells. Our study indicates that the alternative splicing of CSF-1 mRNA 3′UTR can regulate differential secretion of CSF-1 protein.

Original languageEnglish (US)
Pages (from-to)1004-1010
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume525
Issue number4
DOIs
StatePublished - May 14 2020

Keywords

  • CSF-1 differential secretion
  • HuR
  • Var-1 long 3′UTR
  • Var-4 short 3′UTR

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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