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, Verlagsversion
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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 |
Ort: | Darmstadt |
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://tuprints.ulb.tu-darmstadt.de/11599 |
Zugehörige Links: | |
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. |
Status: | Verlagsversion |
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: | 09 Aug 2024 06:54 |
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