Functional proteomics identifies miRNAs to target a p27/Myc/phospho-Rb signature in breast and ovarian cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-02

AUTHORS

E G Seviour, V Sehgal, Y Lu, Z Luo, T Moss, F Zhang, S M Hill, W Liu, S N Maiti, L Cooper, R Azencot, G Lopez-Berestein, C Rodriguez-Aguayo, R Roopaimoole, C Pecot, A K Sood, S Mukherjee, J W Gray, G B Mills, P T Ram

ABSTRACT

The myc oncogene is overexpressed in almost half of all breast and ovarian cancers, but attempts at therapeutic interventions against myc have proven to be challenging. Myc regulates multiple biological processes, including the cell cycle, and as such is associated with cell proliferation and tumor progression. We identified a protein signature of high myc, low p27 and high phospho-Rb significantly correlated with poor patient survival in breast and ovarian cancers. Screening of a miRNA library by functional proteomics in multiple cell lines and integration of data from patient tumors revealed a panel of five microRNAs (miRNAs) (miR-124, miR-365, miR-34b*, miR-18a and miR-506) as potential tumor suppressors capable of reversing the p27/myc/phospho-Rb protein signature. Mechanistic studies revealed an RNA-activation function of miR-124 resulting in direct induction of p27 protein levels by binding to and inducing transcription on the p27 promoter region leading to a subsequent G1 arrest. Additionally, in vivo studies utilizing a xenograft model demonstrated that nanoparticle-mediated delivery of miR-124 could reduce tumor growth and sensitize cells to etoposide, suggesting a clinical application of miRNAs as therapeutics to target the functional effect of myc on tumor growth. More... »

PAGES

691

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2014.469

DOI

http://dx.doi.org/10.1038/onc.2014.469

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008589321

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25639871


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