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Epigenetic inhibitors upregulate expression of MGAT3 in HepG2 cells and cause significant changes in glycosylation of secreted proteins (608.2)
Author(s) -
Zoldos Vlatka,
Horvat Tomislav,
Korac Petra,
Klasić Marija,
Markulin Dora,
Kristic Jasminka,
Lauc Gordan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.608.2
Subject(s) - fucosylation , glycosylation , epigenetics , glycome , biology , dna methylation , gene , glycan , downregulation and upregulation , microbiology and biotechnology , gene expression , biochemistry , glycoprotein
Protein glycosylation is a ubiquitous modification which affects protein structure and function. The majority of blood proteins are synthesized and glycosylated in the liver. Changes in plasma protein glycosylation are often associated with different types of liver disease, including hepatocellular carcinoma (HCC). Interestingly, secretomes of HCC patients and of HepG2 cells in culture are comparable, making this cell line an appropriate model to study how induced epigenetic changes can affect glycosylation of secreted proteins. We have correlated global changes in the expression 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. Using Human RT Profiler glycosylation qPCR array that contains 94 known glyco‐genes we identified that 20% of these genes are regulated by DNA methylation, and this regulation was reflected on glycan profile of secreted proteins from Hepg2 cells. The majority of changes in the glycosylation profile could be attributed to changed expression of Mgat3 responsible for addition of bisecting GlcNAc, which prevents further fucosylation and branching. We further confirmed its role in plasma glycome by targeted modulation of Mgat3 expression with epigenetic inhibitors. 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. Grant Funding Source : Supported by European Commission grants IBD‐BIOM and IntegraLife