Z Gastroenterol 2020; 58(01): e49
DOI: 10.1055/s-0039-3402233
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

Analysis of the expression and function of KIAA1199 in hepatocellular carcinoma

T Melzer
1   Friedrich-Alexander-University Erlangen-Nürnberg, Institute of Biochemistry, Erlangen, Germany
,
J Sommer
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   Friedrich-Alexander-University Erlangen-Nürnberg, Comprehensive Cancer Center, CCC Erlangen-EMN, Erlangen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

 

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Especially at advanced stages, therapeutic options are very limited. KIAA1199 is a protein that has been shown to participate in several cellular signaling pathways as well as cell proliferation. It has been described as tumor promoter but also as tumor suppressor depending on the type of cancer.

The aim of this project was to analyze the expression and function of KIAA1199 in HCC.

Methods and Results:

Human HCC cell lines (HepG2, Hep3B and PLC cells) showed reduced KIAA1199 protein expression compared to primary human hepatocytes. RT-qPCR analysis showed a downregulation of KIAA1199 in human HCC specimens compared to corresponding adjacent non-tumorous liver tissue. The observed downregulation was also confirmed by immunostaining of a tissue microarray consisting of paired tumor and non-tumorous liver tissues of HCC patients. As revealed by immunofluorescence, hepatic KIAA1199 is predominantly located in the cytoplasm of the HCC cells. Analysis of HCC patient data showed that KIAA1199 expression was lower in high risk patient group (based on prognostic index) and correlated inversely with patients' survival. Treatment with the HDAC inhibitor trichostatin A affected KIAA1199 expression in HCC cells, indicating epigenetic regulation. Interestingly, also treatment with sorafenib caused an upregulation of KIAA1199 expression in HCC cells. In order to assess the effect of KIAA1199 on HCC cell proliferation, its expression was suppressed applying specific siRNA in HCC cell lines. Subsequently, cell proliferation analyses as well as clonogenic assays were performed. Surprisingly, HCC cells transfected with KIAA1199 siRNA showed significantly decreased proliferation, which was accompanied by decreased CyclinD1 mRNA expression. Furthermore, KIAA1199-suppressed HCC cells revealed decreased colony formation ability compared to cells transfected with control siRNA.

Summary and conclusion:

KIAA1199 expression is downregulated in HCC, indicating an anti-tumorigenic role. In contrast to that, functional analyses in si-transfected HCC cells revealed a pro-proliferative effect of the protein. Thus, the role of KIAA1199 in HCC seems to be of complex nature, and requires further investigation.