Z Gastroenterol 2018; 56(08): e309
DOI: 10.1055/s-0038-1668941
Kurzvorträge
Gastroenterologische Onkologie
HCC: Molekulare Grundlagen der Karzinogenese und des therapeutischen Targetings – Donnerstag, 13. September 2018, 12:00 – 13:52, 22b
Georg Thieme Verlag KG Stuttgart · New York

Expression and functions of PRRX1 in hepatocellular carcinoma

W Piorońska
1   Medical Faculty Mannheim, Heidelberg University, Department of Medicine II, Molecular Hepatology Section, Mannheim, Deutschland
,
ZC Nwosu
1   Medical Faculty Mannheim, Heidelberg University, Department of Medicine II, Molecular Hepatology Section, Mannheim, Deutschland
,
MP Ebert
1   Medical Faculty Mannheim, Heidelberg University, Department of Medicine II, Molecular Hepatology Section, Mannheim, Deutschland
,
S Dooley
1   Medical Faculty Mannheim, Heidelberg University, Department of Medicine II, Molecular Hepatology Section, Mannheim, Deutschland
,
C Meyer
1   Medical Faculty Mannheim, Heidelberg University, Department of Medicine II, Molecular Hepatology Section, Mannheim, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2018 (online)

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    Background and aims:

    Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death. Paired related homeobox 1 (PRRX1) is a transcriptional co-activator, which regulates cell growth and differentiation. Whether PRRX1 has a functional relevance in HCC is still unknown. We performed an in-depth analysis of PRRX1 expression, and mechanistically validate its function in HCC.

    Methods:

    The expression of PRRX1 in human HCC was assessed in online databases, including Oncomine and cBioPortal, as well as in microarray datasets encompassing > 1,200 liver tumour profiles. We also applied a bioinformatics approach to analyse functional annotation of genes correlated with PRRX1 in HCC. In vitro, PRRX1 expression was analysed in HCC cell lines. Further, PRRX1 expression was modulated by siRNA and overexpression, followed by functional assays on proliferation, clonogenicity as well as biochemical parameters.

    Results:

    PRRX1 is frequently upregulated in human HCC. Its expression did not predict overall survival and there was no significant difference in clinical parameters (e.g. tumour size, ALT, AFP) when tumours with low PRRX1 were compared with those showing higher expression in the GSE14520 dataset. Pathway annotation analysis identified extracellular matrix activities, Akt signaling, focal adhesion and metabolism as processes strongly associated with PRRX1 in clinical tissues. In cell lines, PRRX1 expression was variable, being higher in cells that display epithelial morphology. Intriguingly, knockdown of PRRX1 led to higher proliferation and clonogenicity, whereas overexpression reduced these phenotypes. Knockdown increased glucose consumption and significantly impacted on cell migration regardless of its basal expression in the cell lines, suggesting functional importance.

    Conclusion:

    Our findings provide evidence for a functional role of PRRX1 in HCC, including the potential to control pathways that facilitate tumour progression.


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