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  • Emmerich, Anne C.Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany (author)

Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-03-13
  • Frontiers Media SA,2020
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-410125
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-410125URI
  • https://doi.org/10.3389/fphar.2020.00196DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:143404022URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • MicroRNAs (miRs) are one of the most important post-transcriptional repressors of gene expression. However, miR-574-5p has recently been shown to positively regulate the expression of microsomal prostaglandin E-synthase-1 (mPGES-1), a key enzyme in the prostaglandin E2 (PGE2) biosynthesis, by acting as decoy to the RNA-binding protein CUG-RNA binding protein 1 (CUGBP1) in human lung cancer. miR-574-5p exhibits oncogenic properties and promotes lung tumor growth in vivo via induction of mPGES-1-derived PGE2 synthesis. In a mass spectrometry-based proteomics study, we now attempted to characterize this decoy mechanism in A549 lung cancer cells at a cellular level. Besides the identification of novel CUGBP1 targets, we identified that the interaction between miR-574-5p and CUGBP1 specifically regulates mPGES-1 expression. This is supported by the fact that CUGBP1 and miR-574-5p are located in the nucleus, where CUGBP1 regulates alternative splicing. Further, in a bioinformatical approach we showed that the decoy-dependent mPGES-1 splicing pattern is unique. The specificity of miR-574-5p/CUGBP1 regulation on mPGES-1 expression supports the therapeutic strategy of pharmacological inhibition of PGE2 formation, which may provide significant therapeutic value for NSCLC patients with high miR-574-5p levels.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Wellstein, JuliaTech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany (author)
  • Ossipova, ElenaKarolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumator Unit, Stockholm, Sweden (author)
  • Baumann, IsabelTech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany (author)
  • Lengqvists, JohanKarolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumator Unit, Stockholm, Sweden (author)
  • Kultima, KimUppsala universitet,Klinisk kemi(Swepub:uu)kikul535 (author)
  • Jakobsson, Per-JohanKarolinska Institutet (author)
  • Steinhilber, DieterGoethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany (author)
  • Saul, Meike J.Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany (author)
  • Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, GermanyKarolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumator Unit, Stockholm, Sweden (creator_code:org_t)

Related titles

  • In:Frontiers in Pharmacology: Frontiers Media SA111663-9812

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