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

FASEB J. 2019 Jun;33(6):6933-6947. doi: 10.1096/fj.201802547R. Epub 2019 Mar 28.


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.

Keywords: A549 cells; PGE; alternative splicing; lung cancer; prostaglandins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • CELF1 Protein / genetics
  • CELF1 Protein / metabolism*
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic / drug effects
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Mimicry
  • Neoplasms, Experimental
  • Prostaglandin-E Synthases / genetics
  • Prostaglandin-E Synthases / metabolism*
  • Protein Binding
  • Protein Synthesis Inhibitors / pharmacology
  • Puromycin / pharmacology
  • RNA / genetics
  • RNA / metabolism*
  • RNA Interference
  • RNA Isoforms
  • RNA, Messenger


  • CELF1 Protein
  • CELF1 protein, human
  • MIRN574 microRNA, human
  • MicroRNAs
  • Protein Synthesis Inhibitors
  • RNA Isoforms
  • RNA, Messenger
  • Puromycin
  • RNA
  • PTGES protein, human
  • Prostaglandin-E Synthases