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miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction.

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), pp. 6933-6947. ISSN 1530-6860,
DOI: 10.1096/fj.201802547R,
[Article]

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.

Item Type: Article
Erschienen: 2019
Creators: 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
Title: miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction.
Language: English
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.

Journal or Publication Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Journal volume: 33
Number: 6
Divisions: 10 Department of Biology
10 Department of Biology > Synthetic Genetic Circuits
Date Deposited: 15 Apr 2019 09:40
DOI: 10.1096/fj.201802547R
Identification Number: pmid:30922080
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