Tarek Kröhler, Sonja Keßler, Kevan Hosseini, Markus List, Ahmad Barghash, Sonika Patial, Stephan Laggai, Katja Gemperlein, Johannes Haybäck, Rolf Müller, Volkhard Helms, Marcel Holger Schulz, Jessica Hoppstädter, Perry J. Blackshear, Alexandra Kathrin Kiemer
- Hepatic lipid deposition and inflammation represent risk factors for hepatocellular carcinoma (HCC). The mRNA-binding protein tristetraprolin (TTP, gene name ZFP36) has been suggested as a tumor suppressor in several malignancies, but it increases insulin resistance. The aim of this study was to elucidate the role of TTP in hepatocarcinogenesis and HCC progression. Employing liver-specific TTP-knockout (lsTtp-KO) mice in the diethylnitrosamine (DEN) hepatocarcinogenesis model, we observed a significantly reduced tumor burden compared to wild-type animals. Upon short-term DEN treatment, modelling early inflammatory processes in hepatocarcinogenesis, lsTtp-KO mice exhibited a reduced monocyte/macrophage ratio as compared to wild-type mice. While short-term DEN strongly induced an abundance of saturated and poly-unsaturated hepatic fatty acids, lsTtp-KO mice did not show these changes. These findings suggested anti-carcinogenic actions of TTP deletion due to effects on inflammation and metabolism. Interestingly, though, investigating effects of TTP on different hallmarks of cancer suggested tumor-suppressing actions: TTP inhibited proliferation, attenuated migration, and slightly increased chemosensitivity. In line with a tumor-suppressing activity, we observed a reduced expression of several oncogenes in TTP-overexpressing cells. Accordingly, ZFP36 expression was downregulated in tumor tissues in three large human data sets. Taken together, this study suggests that hepatocytic TTP promotes hepatocarcinogenesis, while it shows tumor-suppressive actions during hepatic tumor progression.
MetadatenAuthor: | Tarek Kröhler, Sonja KeßlerORCiDGND, Kevan Hosseini, Markus ListORCiDGND, Ahmad Barghash, Sonika Patial, Stephan Laggai, Katja Gemperlein, Johannes Haybäck, Rolf MüllerORCiDGND, Volkhard HelmsORCiDGND, Marcel Holger SchulzORCiDGND, Jessica HoppstädterORCiDGND, Perry J. Blackshear, Alexandra Kathrin KiemerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-518336 |
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DOI: | https://doi.org/10.3390/cancers11111754 |
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ISSN: | 2072-6694 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31717307 |
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Parent Title (English): | Cancers |
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Publisher: | MDPI |
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Place of publication: | Basel |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2019 |
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Date of first Publication: | 2019/11/08 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2020/02/10 |
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Tag: | BCL2; HepG2; Huh7; MYC; NASH; NEAT1; VEGFA; chemoresistance; flow cytometry; liver cancer |
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Volume: | 11 |
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Issue: | 11, Art. 1754 |
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Page Number: | 19 |
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First Page: | 1 |
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Last Page: | 19 |
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Note: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
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HeBIS-PPN: | 46139622X |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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