Please use this identifier to cite or link to this item: doi:10.22028/D291-28124
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Title: The long non-coding RNA H19 suppresses carcinogenesis and chemoresistance in hepatocellular carcinoma
Author(s): Schultheiss, Christina S.
Laggai, Stephan
Czepukojc, Beate
Hussein, Usama K.
List, Markus
Barghash, Ahmad
Tierling, Sascha
Hosseini, Kevan
Golob-Schwarzl, Nicole
Pokorny, Juliane
Hachenthal, Nina
Schulz, Marcel
Helms, Volkhard
Walter, Jörn Erik
Zimmer, Vincent
Lammert, Frank
Bohle, Rainer M.
Dandolo, Luisa
Haybaeck, Johannes
Kiemer, Alexandra
Kessler, Sonja M.
Language: English
Title: Cell Stress
Volume: 1
Issue: 1
Startpage: 37
Endpage: 54
Publisher/Platform: Shared Science Publishers OG
Year of Publication: 2017
Publikation type: Journal Article
Abstract: The long non-coding RNA (lncRNA) H19 represents a maternally expressed and epigenetically regulated imprinted gene product and is discussed to have either tumor-promoting or tumor-suppressive actions. Recently, H19 was shown to be regulated under inflammatory conditions. Therefore, aim of this study was to determine the function of H19 in hepatocellular carcinoma (HCC), an inflammation-associated type of tumor. In four different human HCC patient cohorts H19 was distinctly downregulated in tumor tissue compared to normal or non-tumorous adjacent tissue. We therefore determined the action of H19 in three different human hepatoma cell lines (HepG2, Plc/Prf5, and Huh7). Clonogenicity and proliferation assays showed that H19 overexpression could suppress tumor cell survival and proliferation after treatment with either sorafenib or doxorubicin, suggesting chemosensitizing actions of H19. Since HCC displays a highly chemoresistant tumor entity, cell lines resistant to doxorubicin or sorafenib were established. In all six chemoresistant cell lines H19 expression was significantly downregulated. The promoter methylation of the H19 gene was significantly different in chemoresistant cell lines compared to their sensitive counterparts. Chemoresistant cells were sensitized after H19 overexpression by either increasing the cytotoxic action of doxorubicin or decreasing cell proliferation upon sorafenib treatment. An H19 knockout mouse model (H19Δ3) showed increased tumor development and tumor cell proliferation after treatment with the carcinogen diethylnitrosamine (DEN) independent of the reciprocally imprinted insulin-like growth factor 2 (IGF2). In conclusion, H19 suppresses hepatocarcinogenesis, hepatoma cell growth, and HCC chemoresistance. Thus, mimicking H19 action might be a potential target to overcome chemoresistance in future HCC therapy.
DOI of the first publication: 10.15698/cst2017.10.105
Link to this record: hdl:20.500.11880/27486
http://dx.doi.org/10.22028/D291-28124
ISSN: 2523-0204
Date of registration: 13-Jul-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Collections:UniBib – Die Universitätsbibliographie

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