Saul, Meike J. ; Baumann, Isabell ; Bruno, Annalisa ; Emmerich, Anne C. ; Wellstein, Julia ; Ottinger, Sarah M. ; Contursi, Annalisa ; Dovizio, Melania ; Donnini, Sandra ; Tacconelli, Stefania ; Raouf, Joan ; Idborg, Helena ; Stein, Stefan ; Korotkova, Marina ; Savai, Rajkumar ; Terzuoli, Erika ; Sala, Gianluca ; Seeger, Werner ; Jakobsson, Per-Johan ; Patrignani, Paola ; Suess, Beatrix ; Steinhilber, Dieter (2019)
miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction.
In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33 (6)
doi: 10.1096/fj.201802547R
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
MicroRNAs (miRs) are important posttranscriptional regulators of gene expression. Besides their well-characterized inhibitory effects on mRNA stability and translation, miRs can also activate gene expression. In this study, we identified a novel noncanonical function of miR-574-5p. We found that miR-574-5p acts as an RNA decoy to CUG RNA-binding protein 1 (CUGBP1) and antagonizes its function. MiR-574-5p induces microsomal prostaglandin E synthase-1 (mPGES-1) expression by preventing CUGBP1 binding to its 3'UTR, leading to an enhanced alternative splicing and generation of an mPGES-1 3'UTR isoform, increased mPGES-1 protein expression, PGE formation, and tumor growth in vivo. miR-574-5p-induced tumor growth in mice could be completely inhibited with the mPGES-1 inhibitor CIII. Moreover, miR-574-5p is induced by IL-1β and is strongly overexpressed in human nonsmall cell lung cancer where high mPGES-1 expression correlates with a low survival rate. The discovered function of miR-574-5p as a CUGBP1 decoy opens up new therapeutic opportunities. It might serve as a stratification marker to select lung tumor patients who respond to the pharmacological inhibition of PGE formation.-Saul, M. J., Baumann, I., Bruno, A., Emmerich, A. C., Wellstein, J., Ottinger, S. M., Contursi, A., Dovizio, M., Donnini, S., Tacconelli, S., Raouf, J., Idborg, H., Stein, S., Korotkova, M., Savai, R., Terzuoli, E., Sala, G., Seeger, W., Jakobsson, P.-J., Patrignani, P., Suess, B., Steinhilber, D. miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2019 |
| Autor(en): | Saul, Meike J. ; Baumann, Isabell ; Bruno, Annalisa ; Emmerich, Anne C. ; Wellstein, Julia ; Ottinger, Sarah M. ; Contursi, Annalisa ; Dovizio, Melania ; Donnini, Sandra ; Tacconelli, Stefania ; Raouf, Joan ; Idborg, Helena ; Stein, Stefan ; Korotkova, Marina ; Savai, Rajkumar ; Terzuoli, Erika ; Sala, Gianluca ; Seeger, Werner ; Jakobsson, Per-Johan ; Patrignani, Paola ; Suess, Beatrix ; Steinhilber, Dieter |
| Art des Eintrags: | Bibliographie |
| Titel: | miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction. |
| Sprache: | Englisch |
| Publikationsjahr: | Juni 2019 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
| Jahrgang/Volume einer Zeitschrift: | 33 |
| (Heft-)Nummer: | 6 |
| DOI: | 10.1096/fj.201802547R |
| Kurzbeschreibung (Abstract): | MicroRNAs (miRs) are important posttranscriptional regulators of gene expression. Besides their well-characterized inhibitory effects on mRNA stability and translation, miRs can also activate gene expression. In this study, we identified a novel noncanonical function of miR-574-5p. We found that miR-574-5p acts as an RNA decoy to CUG RNA-binding protein 1 (CUGBP1) and antagonizes its function. MiR-574-5p induces microsomal prostaglandin E synthase-1 (mPGES-1) expression by preventing CUGBP1 binding to its 3'UTR, leading to an enhanced alternative splicing and generation of an mPGES-1 3'UTR isoform, increased mPGES-1 protein expression, PGE formation, and tumor growth in vivo. miR-574-5p-induced tumor growth in mice could be completely inhibited with the mPGES-1 inhibitor CIII. Moreover, miR-574-5p is induced by IL-1β and is strongly overexpressed in human nonsmall cell lung cancer where high mPGES-1 expression correlates with a low survival rate. The discovered function of miR-574-5p as a CUGBP1 decoy opens up new therapeutic opportunities. It might serve as a stratification marker to select lung tumor patients who respond to the pharmacological inhibition of PGE formation.-Saul, M. J., Baumann, I., Bruno, A., Emmerich, A. C., Wellstein, J., Ottinger, S. M., Contursi, A., Dovizio, M., Donnini, S., Tacconelli, S., Raouf, J., Idborg, H., Stein, S., Korotkova, M., Savai, R., Terzuoli, E., Sala, G., Seeger, W., Jakobsson, P.-J., Patrignani, P., Suess, B., Steinhilber, D. miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction. |
| ID-Nummer: | pmid:30922080 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Synthetic Genetic Circuits (2020 umbenannt in "Synthetic RNA biology") |
| Hinterlegungsdatum: | 15 Apr 2019 09:40 |
| Letzte Änderung: | 26 Aug 2019 09:36 |
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