miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction
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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.
In: FASEB J, Vol. 33, No. 6, 06.2019, p. 6933-6947.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - miR-574-5p as RNA decoy for CUGBP1 stimulates human lung tumor growth by mPGES-1 induction
AU - Saul, Meike J
AU - Baumann, Isabell
AU - Bruno, Annalisa
AU - Emmerich, Anne C
AU - Wellstein, Julia
AU - Ottinger, Sarah M
AU - Contursi, Annalisa
AU - Dovizio, Melania
AU - Donnini, Sandra
AU - Tacconelli, Stefania
AU - Raouf, Joan
AU - Idborg, Helena
AU - Stein, Stefan
AU - Korotkova, Marina
AU - Savai, Rajkumar
AU - Terzuoli, Erika
AU - Sala, Gianluca
AU - Seeger, Werner
AU - Jakobsson, Per-Johan
AU - Patrignani, Paola
AU - Suess, Beatrix
AU - Steinhilber, Dieter
PY - 2019/6
Y1 - 2019/6
N2 - 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, PGE2 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 PGE2 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.
AB - 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, PGE2 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 PGE2 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.
KW - A549 Cells
KW - Animals
KW - CELF1 Protein/genetics
KW - Cell Proliferation
KW - Gene Expression Regulation, Neoplastic/drug effects
KW - HeLa Cells
KW - Humans
KW - Mice
KW - Mice, Nude
KW - MicroRNAs/genetics
KW - Molecular Mimicry
KW - Neoplasms, Experimental
KW - Prostaglandin-E Synthases/genetics
KW - Protein Binding
KW - Protein Synthesis Inhibitors/pharmacology
KW - Puromycin/pharmacology
KW - RNA/genetics
KW - RNA Interference
KW - RNA Isoforms
KW - RNA, Messenger
U2 - 10.1096/fj.201802547R
DO - 10.1096/fj.201802547R
M3 - SCORING: Journal article
C2 - 30922080
VL - 33
SP - 6933
EP - 6947
JO - FASEB J
JF - FASEB J
SN - 0892-6638
IS - 6
ER -