Post-transcriptional regulation of mPGES-1 by the balance between CUGBP1 and miR-574-5p

• Main Author: Baumann, Isabell
• Format: Others
• Language: en
• Published: 2017
• Online Access: https://tuprints.ulb.tu-darmstadt.de/6041/1/Doktorarbeit%20Isabell%20Baumann_3.3..pdf; Baumann, Isabell <http://tuprints.ulb.tu-darmstadt.de/view/person/Baumann=3AIsabell=3A=3A.html> (2017): Post-transcriptional regulation of mPGES-1 by the balance between CUGBP1 and miR-574-5p.Darmstadt, Technische Universität, [Ph.D. Thesis]

Prostaglandin E2 (PGE2) is a bioactive lipid delivered from the arachidonic acid cascade that can elicit a wide range of biological effects associated with inflammatory disorders and different kinds of cancer. The microsomal prostaglandin E2 synthase-1 (mPGES-1) is the terminal enzyme in the induced PGE2 biosynthesis, which is markedly upregulated by pro-inflammatory stimuli in lung cancer. Different studies showed that mPGES-1 promoter alone cannot account for the strong induction by cytokines suggesting that additional namely post-transcriptional regulation mechanism might be involved. Recently, we could show that mPGES-1 mRNA splicing and degradation is regulated by CUG-binding protein 1 (CUGBP1) in A549 lung cancer cells. Furthermore, we demonstrated that the mPGES-1 translation is repressed by CUGBP1 in this type of cancer cells. The function of CUGBP1 is regulated by its localization and phosphorylation status. In addition to this, we identified another CUGBP1 regulation mechanism, whereby a miRNA may act as RNA decoy to CUGBP1 binding. Interestingly, the upregulation of this miRNA confers with an enhanced tumor progression and correlates with an elevated mPGES-1 expression in human lung cancer. New knowledge of mPGES-1 regulation and the characterization of novel mPGES-1 splice variant will provide a better understanding and characterization of disease development and may lead to the discovery of new therapeutic targets addressing the regulation of mPGES-1 splicing.