Posttranscriptional Suppression of Proto-Oncogene c -fms Expression by Vigilin in Breast Cancer

Abstract

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.