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Epigenetic modulation of N-glycome excreted from HepG2 liver cells in culture

Protein glycosylation is a ubiquitous modification which affects protein structure and function. The majority of blood proteins, except gamma globulins, are prior to secretion synthesized and glycosylated in liver. Changes in their N- glycosylation are often associated with emergence and development of various liver diseases, including hepatocellular carcinoma (HCC). Interestingly, secretomes of HCC patients and of hepatoma-derived cells in culture (HepG2) are comparable, making this cell line an appropriate model to study how induced epigenetic changes can affect N- glycosylation of secreted proteins. We correlated changes in the expression levels of glyco-genes with preferential appearance of particular glycan structures in the HepG2 secretome following the treatment of HepG2 cells with DNA methylation and histone deacetylation inhibitors. In addition, we focused on hepatocyte nuclear factor 1A gene (HNF1A), coding for a transcription factor involved in regulation of many liver-specific genes as well as fucosylation and branching of plasma N-glycans. Therefore, we investigated whether induced changes in HNF1A expression affect the composition of HepG2 secretome/glycome. Given that many epigenetic inhibitors are currently explored as a therapeutic strategy in treatment of cancer, the presented work contributes to our understanding of their efficiency in altering the N-glycan profiles of secreted proteins.

DNA methylation ; N glycosylation ; 5-aza-2-deoxycytidine ; HepG2

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