{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T20:50:05Z","timestamp":1784580605607,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T00:00:00Z","timestamp":1573171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers11111754","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T11:30:19Z","timestamp":1573212619000},"page":"1754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The mRNA-binding Protein TTP\/ZFP36 in Hepatocarcinogenesis and Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"11","author":[{"given":"Tarek","family":"Kr\u00f6hler","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8591-851X","authenticated-orcid":false,"given":"Sonja M.","family":"Kessler","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbr\u00fccken, Germany"},{"name":"Institute of Pharmacy, Department of Pharmacology for Natural Sciences, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevan","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-4168","authenticated-orcid":false,"given":"Markus","family":"List","sequence":"additional","affiliation":[{"name":"Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarland Informatics Campus, 66123 Saarbr\u00fccken, Germany"},{"name":"Big Data in BioMedicine Group, Chair of Experimental Bioinformatics, TUM School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Barghash","sequence":"additional","affiliation":[{"name":"School of Electrical Engineering and Information Technology, German Jordanian University, Amman 11180, Jordan"},{"name":"Center for Bioinformatics, Saarland University, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonika","family":"Patial","sequence":"additional","affiliation":[{"name":"The Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"},{"name":"Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Laggai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Gemperlein","sequence":"additional","affiliation":[{"name":"Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Haybaeck","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, 39106 Magdeburg, Germany"},{"name":"Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck,  Innsbruck 6020, Austria"},{"name":"Institute of Pathology, Medical University of Graz,  Graz 8036, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-9154","authenticated-orcid":false,"given":"Volkhard","family":"Helms","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics, Saarland University, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel H.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarland Informatics Campus, 66123 Saarbr\u00fccken, Germany"},{"name":"Cluster of Excellence in Multimodal Computing and Interaction, Saarland Informatics Campus, 66123 Saarbr\u00fccken, Germany"},{"name":"Institute for Cardiovascular Regeneration, Goethe-University Hospital, 60590 Frankfurt, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner site Rhine-Main, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Hoppst\u00e4dter","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry J.","family":"Blackshear","sequence":"additional","affiliation":[{"name":"The Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7224-9900","authenticated-orcid":false,"given":"Alexandra 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