Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3'UTR element in CSF-1R mRNA.

Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3'UTR element in CSF-1R mRNA. Transl Oncol. 2018 Oct 03;12(1):106-115 Authors: Woo HH, Lee SC, Stoffer JB, Rush D, Chambers SK Abstract Vigilin, a nucleocytoplasmic shuttling protein, post-transcriptionally suppresses proto-oncogene c-fms expression (encoding CSF-1R) in breast cancer by binding to a 69 nt cis-acting 3-UTR element in CSF-1R mRNA. CSF-1R is an important mediator of breast cancer development, metastasis, and survival. We confirm that vigilin decreases in vitro reporter luciferase activity as well as the translation rate of target mRNAs. We further explore the mechanism of suppression of CSF-1R. We show that the 69 nt binding element has profound effects on translation efficiency of CSF-1R mRNA, not seen in the presence of mutation of the element. Also, mutation of the 69 nt element in the CSF-1R mRNA 3'UTR both interferes with direct vigilin binding and obviates effect of vigilin overexpression on translational repression of CSF-1R. We show that stable vigilin binding requires the full length 69 nt CSF-1R element, including the 26 nt pyrimidine-rich core. Furthermore, titration of endogenous vigilin and other proteins which bind the 69 nt element, by exogenously introduced CSF-1R mRNA 3'UTR containing the pyrimidine-rich sequence, increases the adhesion, motility, and invasion of breast cancer cells. This phenotypic effect is not seen when the 69 n...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Tags: Transl Oncol Source Type: research