title: DNA hypomethylation upregulates expression of the MGAT3 gene in HepG2 cells and leads to changes in N-glycosylation of secreted glycoproteins.
abstract: Changes in N-glycosylation of plasma proteins are observed in many types of cancer, nevertheless, few studies suggest the exact mechanism involved in aberrant protein glycosylation. Here we studied the impact of DNA methylation on the N-glycome in the secretome of the HepG2 cell line derived from hepatocellular carcinoma (HCC). Since the majority of plasma glycoproteins originate from the liver, the HepG2 cells represent a good model for glycosylation changes in HCC that are detectable in blood, which is an easily accessible analytic material in a clinical setting. Two different concentrations of 5-aza-2'-deoxycytidine (5-aza-2dC) differentially affected global genome methylation and induced different glycan changes. Around twenty percent of 84 glyco-genes analysed changed expression level after the 5-aza-2dC treatment as a result of global genome hypomethylation. A correlation study between the changes in glyco-gene expression and the HepG2 glycosylation profile suggests that the MGAT3 gene might be responsible for the glycan changes consistently induced by both doses of 5-aza-2dC. Core-fucosylated tetra-antennary structures were decreased in quantity likely as a result of hypomethylated MGAT3 gene promoter followed by increased expression of this gene.
authors.affiliation: University of Zagreb Faculty of Science, Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Klasić
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Jasminka
authors.initials: J
authors.lastname: Krištić
authors.affiliation: University of Zagreb Faculty of Science, Zagreb, Croatia.
authors.forename: Petra
authors.initials: P
authors.lastname: Korać
authors.affiliation: University of Zagreb Faculty of Science, Zagreb, Croatia.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Horvat
authors.affiliation: University of Zagreb Faculty of Science, Zagreb, Croatia.
authors.forename: Dora
authors.initials: D
authors.lastname: Markulin
authors.affiliation: University of Zagreb Faculty of Science, Zagreb, Croatia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Vojta
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Karli R
authors.initials: KR
authors.lastname: Reiding
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.|Division of BioAnalytical Chemistry, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.|University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
authors.forename: Gordan
authors.initials: G
authors.lastname: Lauc
authors.affiliation: University of Zagreb Faculty of Science, Zagreb, Croatia.
authors.forename: Vlatka
authors.initials: V
authors.lastname: Zoldoš
mesh_terms: D019175:DNA Methylation; D015870:Gene Expression; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D056945:Hep G2 Cells; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D006023:Glycoproteins; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase