Dokument: Regulation of KIF23 by miR-107 controls replicative tumor cell fitness in mouse and human hepatocellular carcinoma
| Titel: | Regulation of KIF23 by miR-107 controls replicative tumor cell fitness in mouse and human hepatocellular carcinoma | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=68724 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250220-113056-1 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Castoldi, Mirco [Autor] Roy, Sanchari [Autor] Angendohr, Carolin [Autor] Pellegrino, Rossella [Autor] Vucur, Mihael [Autor] Singer, Michael T. [Autor] Buettner, Veronika [Autor] Dille, Matthias [Autor] Wolf, Stephanie D. [Autor] Heij, Lara R. [Autor] | |||||||
| Dateien: |
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| Stichwörter: | tissue microarrays, Liver cancer, Kif23, HDTVi, miR-107 | |||||||
| Beschreibung: | Background & Aims
In hepatocellular carcinoma (HCC), successful translation of experimental targets identified in mouse models to human patients has proven challenging. In this study, we used a comprehensive transcriptomic approach in mice to identify novel potential targets for therapeutic intervention in humans. Methods We analyzed combined genome-wide miRNA and mRNA expression data in three pathogenically distinct mouse models of liver cancer. Effects of target genes on hepatoma cell fitness were evaluated by proliferation, survival and motility assays. TCGA and GEO databases, in combination with tissue microarrays, were used to validate the mouse targets and their impact on human HCC prognosis. Finally, the functional effects of the identified targets on tumorigenesis and tumor therapy were tested in hydrodynamic tail vein injection-based preclinical HCC models in vivo. Results The expression of miR-107 was found to be significantly reduced in mouse models of liver tumors of various etiologies and in cohorts of humans with HCC. Overexpression of miR-107 or inhibition of its novel target kinesin family member 23 (Kif23) significantly reduced proliferation by interfering with cytokinesis, thereby controlling survival and motility of mouse and human hepatoma cells. In humans, KIF23 expression was found to be a prognostic marker in liver cancer, with high expression associated with poor prognosis. Hydrodynamic tail vein injection of vectors carrying either pre-miR-107 or anti-Kif23 shRNA inhibited the development of highly aggressive c-Myc-NRAS-induced liver cancers in mice. Conclusions Disruption of the miR-107/Kif23 axis inhibited hepatoma cell proliferation in vitro and prevented oncogene-induced liver cancer development in vivo, offering a novel potential avenue for the treatment of HCC in humans. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Castoldi, M., Roy, S., Angendohr, C., Pellegrino, R., Vucur, M., Singer, M. T., Büttner, V., Dille, M., Wolf, S. D., Heij, L. R., Ghallab, A., Albrecht, W., Hengstler, J. G., Flügen, G., Knoefel, W. T., Bode, J. G., Zender, L., Neumann, U. P., Heikenwälder, M., … Lüdde, T. (2024). Regulation of KIF23 by miR-107 controls replicative tumor cell fitness in mouse and human hepatocellular carcinoma. Journal of Hepatology, 82(3), 499–511. https://doi.org/10.1016/j.jhep.2024.08.025 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 20.02.2025 | |||||||
| Dateien geändert am: | 20.02.2025 |
