Post-Transcriptional Regulation of Proto-Oncogene c-fms in Breast Cancer

Woo, Ho-Hyung; Chambers, Setsuko K.

doi:10.5772/53541

Cited by 2 publications

(3 citation statements)

References 72 publications

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“…The present data indicates that the 69 nt CSF-1R binding element confers net translational repression, and that the repression effect is very significant in the presence of cellular RNA binding proteins, including vigilin and HuR ( Figure 3 ). We have shown that the affinity of vigilin to this pyrimidine-rich region in the CSF-1R mRNA 3′UTR is at least 3-fold stronger than that of HuR in BT20 breast cancer cells by in vitro competition assay [19] . Thus, this specificity of binding of the 69 nt pyrimidine-rich region to vigilin, may explain why disruption of the pyrimidine-rich sequence appears to more significantly affect vigilin-specific actions, rather than those of HuR.…”

Section: Discussionmentioning

confidence: 94%

“…Translational repression and mRNA decay may be reversible by competing CSF-1R mRNA with other RNA binding proteins. We have previously characterized one of them, HuR, with a competition between vigilin and HuR demonstrated for binding this element, with opposing effects on CSF-1R expression [9] , [13] , [19] . The binding of vigilin to the pyrimidine-rich sequence significantly decreases CSF-1R expression ( Figures 2 and 4 ).…”

Section: Discussionmentioning

confidence: 99%

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

Woo

Lee

Stoffer

et al. 2019

Translational Oncology

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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 nt element is deleted. Lastly, we are the first to show that human breast tissues exhibit strong vigilin expression in normal breast epithelium. Our pilot data suggest decreased vigilin protein expression, along with shift from the nucleus to the cytoplasmic location, in the transition to ductal carcinoma in situ.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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

Woo

Lee

Stoffer

et al. 2019

Translational Oncology

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“…Competition of vigilin with another RBP for a binding site is also the basis for regulation of the proto-oncogene c-fms mRNA in human breast cancer. 4 Here, vigilin competes with HuR, a member of the ELAV family of RBPs, 4,78,79 but in contrast to vitellogenin mRNA, upregulated expression of vigilin induces the destabilization of c-fms mRNA. HuR has been reported to bind and stabilize a number of mRNAs 80 and the competition of the two proteins for the same 69 nt element in the c-fms 3 0 UTR could regulate c-fms mRNA translation and stability.…”

Section: Regulation Of Mrna Stability By Vigilinmentioning

confidence: 99%

A jack of all trades: the RNA‐binding protein vigilin

Cheng

Jansen

2017

WIREs RNA

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The vigilin family of proteins is evolutionarily conserved from yeast to humans and characterized by the proteins' 14 or 15 hnRNP K homology (KH) domains, typically associated with RNA-binding. Vigilin is the largest RNA-binding protein (RBP) in the KH domain-containing family and one of the largest RBP known to date. Since its identification 30 years ago, vigilin has been shown to bind over 700 mRNAs and has been associated with cancer progression and cardiovascular disease. We provide a brief historic overview of vigilin research and outline the proteins' different functions, focusing on maintenance of genome ploidy, heterochromatin formation, RNA export, as well as regulation of translation, mRNA transport, and mRNA stability. The multitude of associated functions is reflected by the large number of identified interaction partners, ranging from tRNAs, mRNAs, ribosomes and ribosome-associated proteins, to histone methyltransferases and DNA-dependent protein kinases. Most of these partners bind to vigilin's carboxyterminus, and the two most C-terminal KH domains of the protein, KH13 and KH14, represent the main mRNA-binding interface. Since the nuclear functions of vigilins in particular are not conserved, we outline a model for the basal functions of vigilins, as well as those which were acquired during the transition from unicellular organisms to metazoa. WIREs RNA 2017, 8:e1448. doi: 10.1002/wrna.1448 For further resources related to this article, please visit the WIREs website.

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Post-Transcriptional Regulation of Proto-Oncogene c-fms in Breast Cancer

Cited by 2 publications

References 72 publications

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

A jack of all trades: the RNA‐binding protein vigilin

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