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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. ; Wellstein, Julia ; Ossipova, Elena ; Baumann, Isabell ; Lengqvist, Johan ; Kultima, Kim ; Jakobsson, Per-Johan ; Steinhilber, Dieter ; 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, 2020, 11
doi: 10.25534/tuprints-00011599
Artikel, Zweitveröffentlichung

Kurzbeschreibung (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.

Typ des Eintrags: Artikel
Erschienen: 2020
Autor(en): Emmerich, Anne C. ; Wellstein, Julia ; Ossipova, Elena ; Baumann, Isabell ; Lengqvist, Johan ; Kultima, Kim ; Jakobsson, Per-Johan ; Steinhilber, Dieter ; Saul, Meike J.
Art des Eintrags: Zweitveröffentlichung
Titel: Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells
Sprache: Englisch
Publikationsjahr: 2020
Publikationsdatum der Erstveröffentlichung: 2020
Verlag: Frontiers
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Frontiers in Pharmacology
Jahrgang/Volume einer Zeitschrift: 11
DOI: 10.25534/tuprints-00011599
URL / URN: https://doi.org/10.3389/fphar.2020.00196
Herkunft: Zweitveröffentlichung aus gefördertem Golden Open Access
Kurzbeschreibung (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.

URN: urn:nbn:de:tuda-tuprints-115995
Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Synthetic RNA biology
Hinterlegungsdatum: 05 Apr 2020 19:55
Letzte Änderung: 25 Jul 2023 08:47
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