TU Darmstadt / ULB / TUbiblio

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

Saul, Meike J. and Baumann, Isabell and Bruno, Annalisa and Emmerich, Anne C. and Wellstein, Julia and Ottinger, Sarah M. and Contursi, Annalisa and Dovizio, Melania and Donnini, Sandra and Tacconelli, Stefania and Raouf, Joan and Idborg, Helena and Stein, Stefan and Korotkova, Marina and Savai, Rajkumar and Terzuoli, Erika and Sala, Gianluca and Seeger, Werner and Jakobsson, Per-Johan and Patrignani, Paola and Suess, Beatrix and 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, pp. 6933-6947, 33, (6), 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. and Baumann, Isabell and Bruno, Annalisa and Emmerich, Anne C. and Wellstein, Julia and Ottinger, Sarah M. and Contursi, Annalisa and Dovizio, Melania and Donnini, Sandra and Tacconelli, Stefania and Raouf, Joan and Idborg, Helena and Stein, Stefan and Korotkova, Marina and Savai, Rajkumar and Terzuoli, Erika and Sala, Gianluca and Seeger, Werner and Jakobsson, Per-Johan and Patrignani, Paola and Suess, Beatrix and 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
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
Export:
Suche nach Titel in: TUfind oder in Google

Optionen (nur für Redakteure)

View Item View Item