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

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

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.

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

Av författaren/redakt...: Emmerich, Anne C ...; Wellstein, Julia; Ossipova, Elena; Baumann, Isabel; Lengqvists, Joha ...; Kultima, Kim; visa fler...; Jakobsson, Per-J ...; Steinhilber, Die ...; Saul, Meike J.; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Farmakologi och ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.