title: MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression.
abstract: MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. Our laboratory recently established that microRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). Herein we identify MGAT4A, OGT, and GALNT13 as targets of miR-424. We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. Knockdown of MGAT4A induces cell cycle arrest through decreasing CCND1 levels. MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. This work provides insight into the regulation of cell cycle progression by specific N-glycan branching patterns.
authors.affiliation: From the Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, New York 10003.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Vaiana
authors.affiliation: From the Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, New York 10003.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kurcon
authors.affiliation: From the Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, New York 10003 lkmahal@nyu.edu.
authors.forename: Lara K
authors.identifier: http://orcid.org/0000-0003-4791-8524
authors.initials: LK
authors.lastname: Mahal
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004794:Enzyme Repression; D017930:Genes, Reporter; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D035683:MicroRNAs / Q000819:agonists / Q000378:metabolism*; D017350:N-Acetylgalactosaminyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C554214:MIRN424 microrna, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D019938:Cyclin D1; D008156:Luciferases; C000607945:MGAT4A protein, human; D017350:N-Acetylgalactosaminyltransferases; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; C000589774:GALNT13 protein, human
keywords: CDC25A; Galectin-3; MGAT5; N-glycan biosynthesis; N-linked glycosylation; cell cycle; complex N-glycans; cyclin D1; glycosylation; microRNA (miRNA)