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WG Translational Oncology
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Head:
Prof. Dr. J. Meike Saul
II Medical Clinic and Polyclinic Oncology, Hematology, Bone Marrow Transplantation with the Department of Pneumology
Location:
Campus Research | Building N27, 4th floor, Room 074 and 080
Contact :
Office:
Lab:
Fax: 040 7410 55563
Staff members:
Dr. Kai Breitwieser (Postdoc)
Maili Luisa Pöls (BTA)
Janina Schlüter (Secretary)
Benjamin Schmidt (Physician)
Coralie Tambon (PhD student in natural sciences)
Main research areas
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MiR-574-5p as a biomarker for the stratification of PGE2-dependent tumors
MiRNAs are a class of small non-coding RNAs that contribute to the post-transcriptional regulation of gene expression. We have identified a new function of miR-574-5p. It is based on an RNA decoy for CUG RNA-binding protein 1 (CUGBP1) and inhibits its function as a repressor of microsomal prostaglandin E synthase 1 (mPGES-1), a key enzyme in prostaglandin biosynthesis. Increased intracellular miR-574-5p expression is directly associated with increased synthesis of prostaglandin E2 (PGE2) (Saul et al, FASEB J 2019), an important proinflammatory lipid mediator. The newly discovered association between miR-574-5p and PGE2 qualifies miR-574-5p as a minimally invasive biomarker to select cancer patients likely to respond to pharmacologic inhibition of PGE2.
The role of extracellular miR-574-5p in the microenvironment of various PGE2-dependent tumors
We investigate whether paracrine mechanisms of miR-574-5p play a crucial role in tumor development. To this end, we analyze whether miR-574-5p is transferred within sEV between cancer cells and cells of the tumor microenvironment to influence tumor progression. We have chosen lung cancer and neuroblastoma as comparable tumor model systems. Both tumor types are PGE2-dependent but differ in the cellular site of PGE2 synthesis (Donzelli et al, JEV 2021; Proestler et al, Front Pharmacol 2023).
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Schematic diagram of the PGE2 feedback loop regulation mediated by miR-574-5p and TLR7/8
The miR-574-5p/CUGBP1 decoy regulates PGE2-biosynthesis intracellularly. High intracellular miR-574-5p induces PGE2-biosynthesis. PGE2 triggers the secretion of miR-574-5p in sEV. In recipient AC cells, sEV-derived miR-574-5p activates TLR7/8 signaling, which leads to decreased miR-574-5p, mPGES-1 and PGE2-levels (Donzelli et al. JEV 2021).
Monitoring the exosomal uptake of HEK 293 cells using live-cell imaging analysis (Hegewald et al. Front Immu-nol 2020).
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Characterization of extracellular vesicles at the single vesicle level
We are developing new strategies to identify biomarkers based on improved phenotyping of sEVs. To ensure valid characterization of sEV populations in different cell types and to perform innovative biomarker studies, we use the NanoImager super-resolution microscope (ONI) and the ExoView R100 platform (Unchained Labs). (Breitwieser et al, I. Int. J. Mol. Sci 2022).