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

Emmerich, Anne C. and Wellstein, Julia and Ossipova, Elena and Baumann, Isabell and Lengqvist, Johan and Kultima, Kim and Jakobsson, Per-Johan and Steinhilber, Dieter and Saul, Meike J. (2020):
Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells.
In: Frontiers in Pharmacology, 11, Frontiers, ISSN 1663-9812,
DOI: 10.25534/tuprints-00011599,
[Online-Edition: https://doi.org/10.3389/fphar.2020.00196],
Secondary publishing via sponsored Golden Open Access, [Article]

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Item Type: Article
Origin: Secondary publishing via sponsored Golden Open Access
Title: Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells
Language: English
Abstract:

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 E2 (PGE2) 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 in vivo via induction of mPGES-1-derived PGE2 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 PGE2 formation, which may provide significant therapeutic value for NSCLC patients with high miR-574-5p levels.

Journal or Publication Title: Frontiers in Pharmacology
Journal volume: 11
Publisher: Frontiers
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Synthetic Genetic Circuits
Date Deposited: 30 Mar 2020 12:07
Last Modified: 30 Mar 2020 12:07
DOI: 10.25534/tuprints-00011599
Official URL: https://doi.org/10.3389/fphar.2020.00196
URN: urn:nbn:de:tuda-tuprints-115995
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/11599
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