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miR‐574‐5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES‐1 induction
Author(s) -
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
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201802547r
Subject(s) - decoy , biology , microrna , rna binding protein , alternative splicing , cancer research , untranslated region , rna , messenger rna , microbiology and biotechnology , cell growth , gene expression , gene , genetics , receptor
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 2 formation, and tumor growth in vivo . miR‐574‐5p–induced tumor growth in mice could be completely inhibited with the mPGES‐1 inhibitor OIL 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 2 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. FASEB J. 33, 6933–6947 (2019). www.fasebj.org