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Proteomics-Based Ch...
Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells
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- Emmerich, Anne C. (författare)
- Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany
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- Wellstein, Julia (författare)
- Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany
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- Ossipova, Elena (författare)
- Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumator Unit, Stockholm, Sweden
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- Baumann, Isabel (författare)
- Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany
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- Lengqvists, Johan (författare)
- Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumator Unit, Stockholm, Sweden
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- Kultima, Kim (författare)
- Uppsala universitet,Klinisk kemi
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- Jakobsson, Per-Johan (författare)
- Karolinska Institutet
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- Steinhilber, Dieter (författare)
- Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany
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- Saul, Meike J. (författare)
- Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany;Goethe Univ Frankfurt, Inst Pharmaceut Chem, Frankfurt, Germany
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(creator_code:org_t)
- 2020-03-13
- 2020
- Engelska.
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11
- Relaterad länk:
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https://doi.org/10.3...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- miR-574-5p
- CUGBP1
- non-canonical miR function
- decoy
- proteomics
- mPGES-1
- lung cancer
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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