Regulation of colony stimulating factor-1 expression and ovarian cancer cell behavior in vitro by miR-128 and miR-152.
BACKGROUND
Colony stimulating factor-1 (CSF-1) plays an important role in ovarian cancer biology and as a prognostic factor in ovarian cancer. Elevated levels of CSF-1 promote progression of ovarian cancer, by binding to CSF-1R (the tyrosine kinase receptor encoded by c-fms proto-oncogene).Post-transcriptional regulation of CSF-1 mRNA by its 3' untranslated region (3'UTR) has been studied previously. Several cis-acting elements in 3'UTR are involved in post-transcriptional regulation of CSF-1 mRNA. These include conserved protein-binding motifs as well as miRNA targets. miRNAs are 21-23nt single strand RNA which bind the complementary sequences in mRNAs, suppressing translation and enhancing mRNA degradation.


RESULTS
In this report, we investigate the effect of miRNAs on post-transcriptional regulation of CSF-1 mRNA in human ovarian cancer. Bioinformatics analysis predicts at least 14 miRNAs targeting CSF-1 mRNA 3'UTR. By mutations in putative miRNA targets in CSF-1 mRNA 3'UTR, we identified a common target for both miR-128 and miR-152. We have also found that both miR-128 and miR-152 down-regulate CSF-1 mRNA and protein expression in ovarian cancer cells leading to decreased cell motility and adhesion in vitro, two major aspects of the metastatic potential of cancer cells.


CONCLUSIONS
The major CSF-1 mRNA 3'UTR contains a common miRNA target which is involved in post-transcriptional regulation of CSF-1. Our results provide the evidence for a mechanism by which miR-128 and miR-152 down-regulate CSF-1, an important regulator of ovarian cancer.
Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA. hwoo@azcc.arizona.edu
Ho-Hyung
HH
Woo
Csaba F
CF
László
Stephen
S
Greco
Setsuko K
SK
Chambers
D020413:3' Untranslated Regions; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000235:genetics; D019295:Computational Biology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; C000715470:MAS1 protein, human; C545189:MIRN128 microRNA, human; C550856:MIRN152 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D008156:Luciferases