engleski

The role of SPRTN in hepatocellular carcinoma pathogenesis

SPRTN protein mediates the proteolytic cleavage of covalent DNAprotein cross-links (DPCs) during DNA synthesis, thereby maintaining genomic integrity. The involvement of SPRTN in hepatocellular carcinoma (HCC) was discovered in three patients with different SPRTN mutations but the exact mechanism remains to be elucidated. The relationship between the endoplasmic reticulum (ER) stress response, as well as the DNA damage and the pathogenesis of HCC was proven but the correlation of SPRTN in ER stress response was never tested. We aim to evaluate the involvement of SPRTN, DNA damage and ER stress in the pathogenesis of HCC by measuring the genomic expression of SPRTN and other candidate genes and to observe the difference in amounts and localization of SPRTN and other candidate proteins in HCC samples. Additionally, we aim to investigate the possible functional link between SPRTN, DNA damage and ER-stress-response proteins. Research was performed on human samples of HCC and adjacent (control) liver tissue, collected in the Merkur clinical hospital during liver transplantation surgery procedure. These samples were dissected, embedded in paraffin or used for RNA, DNA and protein isolation. The expression of SPRTN and other candidate genes was evaluated by qPCR and RT2 profiler PCR array for DNA damaging signaling pathway. Protein levels in tissues were evaluated by western blot and immunohistochemistry. Samples were evaluated for the SPRTN gene and candidate gene expressions and protein level alterations. Out of 24 ER stress response candidate genes evaluated by qPCR, we found a significant alteration of 22 genes. Immunohistochemistry staining of tissue sections showed an alteration in tested protein level amount. SPRTN protein is involved in the ER stress response pathogenesis of hepatocellular carcinoma development and further study is needed to elucidate the mechanism of this response.

HCC, SPRTN, ER stress

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