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

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 over-expression 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. (C) 2020 Published by Elsevier Inc.