Posttranscriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer.
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.
Woo
Ho-Hyung
HH
Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA. hwoo@azcc.arizona.edu
Yi
Xiaofang
X
Lamb
Tiffany
T
Menzl
Ina
I
Baker
Terri
T
Shapiro
David J
DJ
Chambers
Setsuko K
SK
D020413:3' Untranslated Regions; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016236:Genes, fms; D006801:Humans; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D014176:Protein Biosynthesis; D000090063:Proto-Oncogene Mas; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C075197:high density lipoprotein binding protein