Aleksandar Vojta1, Ivana Samaržija1, Luka Bočkor1, Vlatka Zoldoš2. 1. University of Zagreb Faculty of Science, Department of Biology, Division of Molecular Biology, Horvatovac 102a, HR-10000 Zagreb, Croatia. 2. University of Zagreb Faculty of Science, Department of Biology, Division of Molecular Biology, Horvatovac 102a, HR-10000 Zagreb, Croatia. Electronic address: vzoldos@biol.pmf.hr.
Abstract
BACKGROUND: Most eukaryotic proteins are modified by covalent addition of glycan molecules that considerably influence their function. Aberrant glycosylation is profoundly involved in malignant transformation, tumor progression and metastasis. Some glycan structures are tumor-specific and reflect disturbed glycan biosynthesis pathways. METHODS: We analyzed DNA methylation and expression of 86 glyco-genes in melanoma, hepatocellular, breast and cervical cancers using data from publicly available databases. We also analyzed methylation datasets without the available matching expression data for glyco-genes in lung cancer, and progression of melanoma into lymph node and brain metastases. RESULTS: Ten glyco-genes (GALNT3, GALNT6, GALNT7, GALNT14, MGAT3, MAN1A1, MAN1C1, ST3GAL2, ST6GAL1, ST8SIA3) showing changes in both methylation and expression in the same type of cancer belong to GalNAc transferases, GlcNAc transferases, mannosidases and sialyltransferases, which is in line with changes in glycan structures already reported in the same type of tumors. Some of those genes were additionally identified as potentially valuable for disease prognosis. The MGAT5B gene, so far identified as specifically expressed in brain, emerged as a novel candidate gene that is epigenetically dysregulated in different cancers other than brain cancer. We also report for the first time aberrant expression of the GALNT and MAN genes in cancer by aberrant promoter methylation. CONCLUSIONS: Aberrant expression of glyco-genes due to aberrant promoter methylation could be a way leading to characteristic glycosylation profiles commonly described in cancer. GENERAL SIGNIFICANCE: Methylation status in promoters of candidate glyco-genes might serve as prognostic markers for specific tumors and point to potential novel targets for epigenetic drugs. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.
BACKGROUND: Most eukaryotic proteins are modified by covalent addition of glycan molecules that considerably influence their function. Aberrant glycosylation is profoundly involved in malignant transformation, tumor progression and metastasis. Some glycan structures are tumor-specific and reflect disturbed glycan biosynthesis pathways. METHODS: We analyzed DNA methylation and expression of 86 glyco-genes in melanoma, hepatocellular, breast and cervical cancers using data from publicly available databases. We also analyzed methylation datasets without the available matching expression data for glyco-genes in lung cancer, and progression of melanoma into lymph node and brain metastases. RESULTS: Ten glyco-genes (GALNT3, GALNT6, GALNT7, GALNT14, MGAT3, MAN1A1, MAN1C1, ST3GAL2, ST6GAL1, ST8SIA3) showing changes in both methylation and expression in the same type of cancer belong to GalNAc transferases, GlcNAc transferases, mannosidases and sialyltransferases, which is in line with changes in glycan structures already reported in the same type of tumors. Some of those genes were additionally identified as potentially valuable for disease prognosis. The MGAT5B gene, so far identified as specifically expressed in brain, emerged as a novel candidate gene that is epigenetically dysregulated in different cancers other than brain cancer. We also report for the first time aberrant expression of the GALNT and MAN genes in cancer by aberrant promoter methylation. CONCLUSIONS: Aberrant expression of glyco-genes due to aberrant promoter methylation could be a way leading to characteristic glycosylation profiles commonly described in cancer. GENERAL SIGNIFICANCE: Methylation status in promoters of candidate glyco-genes might serve as prognostic markers for specific tumors and point to potential novel targets for epigenetic drugs. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.
Authors: Ieva Bagdonaite; Emil M H Pallesen; Mathias I Nielsen; Eric P Bennett; Hans H Wandall Journal: Adv Exp Med Biol Date: 2021 Impact factor: 3.650
Authors: Kaitlyn A Dorsett; Michael P Marciel; Jihye Hwang; Katherine E Ankenbauer; Nikita Bhalerao; Susan L Bellis Journal: Glycobiology Date: 2021-06-03 Impact factor: 4.313
Authors: Isabelle Atkins; Ben Kinnersley; Quinn T Ostrom; Karim Labreche; Dora Il'yasova; Georgina N Armstrong; Jeanette E Eckel-Passow; Minouk J Schoemaker; Markus M Nöthen; Jill S Barnholtz-Sloan; Anthony J Swerdlow; Matthias Simon; Preetha Rajaraman; Stephen J Chanock; Joellen Shildkraut; Jonine L Bernstein; Per Hoffmann; Karl-Heinz Jöckel; Rose K Lai; Elizabeth B Claus; Sara H Olson; Christoffer Johansen; Margaret R Wrensch; Beatrice Melin; Robert B Jenkins; Marc Sanson; Melissa L Bondy; Richard S Houlston Journal: Cancer Res Date: 2019-02-01 Impact factor: 12.701
Authors: Marija Klasić; Jasminka Krištić; Petra Korać; Tomislav Horvat; Dora Markulin; Aleksandar Vojta; Karli R Reiding; Manfred Wuhrer; Gordan Lauc; Vlatka Zoldoš Journal: Sci Rep Date: 2016-04-13 Impact factor: 4.379