AUTHOR=Emmerich Anne C. , Wellstein Julia , Ossipova Elena , Baumann Isabell , Lengqvist Johan , Kultima Kim , Jakobsson Per-Johan , Steinhilber Dieter , Saul Meike J. 

TITLE=Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00196

DOI=10.3389/fphar.2020.00196

ISSN=1663-9812

ABSTRACT=<p>MicroRNAs (miRs) are one of the most important post-transcriptional repressors of gene expression. However, miR-574-5p has recently been shown to positively regulate the expression of microsomal prostaglandin E-synthase-1 (mPGES-1), a key enzyme in the prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) biosynthesis, by acting as decoy to the RNA-binding protein CUG-RNA binding protein 1 (CUGBP1) in human lung cancer. miR-574-5p exhibits oncogenic properties and promotes lung tumor growth <italic>in vivo</italic> via induction of mPGES-1-derived PGE<sub>2</sub> synthesis. In a mass spectrometry-based proteomics study, we now attempted to characterize this decoy mechanism in A549 lung cancer cells at a cellular level. Besides the identification of novel CUGBP1 targets, we identified that the interaction between miR-574-5p and CUGBP1 specifically regulates mPGES-1 expression. This is supported by the fact that CUGBP1 and miR-574-5p are located in the nucleus, where CUGBP1 regulates alternative splicing. Further, in a bioinformatical approach we showed that the decoy-dependent mPGES-1 splicing pattern is unique. The specificity of miR-574-5p/CUGBP1 regulation on mPGES-1 expression supports the therapeutic strategy of pharmacological inhibition of PGE<sub>2</sub> formation, which may provide significant therapeutic value for NSCLC patients with high miR-574-5p levels.</p>