Z Gastroenterol 2020; 58(01): e43
DOI: 10.1055/s-0039-3402217
Poster Visit Session IV Tumors: Saturday, February 15, 2020, 8:30 am – 09:15 am, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

Expression and function of Epithelial Splicing Regulatory Protein 1 in hepatocellular carcinoma

L Vorhauer
1   Friedrich-Alexander-University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen, Germany
,
T Seitz
1   Friedrich-Alexander-University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen, Germany
,
C Hellerbrand
1   Friedrich-Alexander-University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen, Germany
2   Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

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    Epithelial-to-mesenchymal transition (EMT) plays a critical role in tumor progression and metastasis. The Epithelial Splicing Regulatory Protein 1 (ESRP1) belongs to the hnRNP family of RNA binding proteins and regulates alternative splicing of a number of genes associated with EMT. However, the expression and function of ESRP1 in hepatocellular carcinoma (HCC) is unknown.

    The aim of this study was to analyze the expression, regulation and function of ESRP1 in HCC.

    Methods and Results:

    ESRP1 expression levels were analyzed in human HCC tissues and cell lines with RT-qPCR and Western blot analysis. ESRP1 expression varied significantly between different human HCC cell lines, with highest expression levels found in Hep3B compared with HepG2 and PLC cells. Fitting to this, comparison of ESRP1 expression levels in human HCC tissues revealed that there are "high" and "low" "ESRP1-expressors". Regarding the regulation of ESRP1 in HCC, we found that stimulation of HCC cells with recombinant TGFβ1, an EMT inductor, decreased ESRP1 expression. Conversely, siRNA-mediated knockdown of the EMT-inducer zink finger E-box binding homeobox 1 (ZEB1) significantly upregulated ESRP1 expression. Interestingly, siRNA-mediated ESRP1 knockdown decreased E-Cadherin expression and upregulated the expression of EMT markers N-Cadherin, Twist and ZEB1. Furthermore, ESRP1 knockdown caused a shift in the expression of splicing variants exon IIIb to exon IIIc of Fibroblast Growth Factor Receptors, which is known to be associated with a more aggressive phenotype of HCC. Moreover, ESRP1 knockdown significantly increased proliferation of Hep3B cells and induced ERK- and Akt-phosphorylation. Conversely, overexpression of ESRP1 in HepG2 and PLC cells decreased ERK- and Akt-activation.

    Summary and Conclusion:

    Decreased ESRP1 expression promotes tumorigenicity and EMT of HCC cells in vitro. Therefore, ESRP1 appears as potential prognostic parameter in HCC.


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