MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression

Christopher A Vaiana, Tomasz Kurcon, Lara K Mahal

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1529-37
Number of pages9
JournalJournal of Biological Chemistry
Volume291
Issue number3
DOIs
StatePublished - Jan 15 2016

Fingerprint

Glycosylation
MicroRNAs
Polysaccharides
Cell Cycle
Cells
Transforming Growth Factors
Cell proliferation
Proxy
Cell death
Cell Cycle Checkpoints
Breast
Cell Death
Epithelial Cells
Cell Proliferation
Cytokines
Cell Line
Enzymes
Proteins
human MIRN424 microrna

Cite this

MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression. / Vaiana, Christopher A; Kurcon, Tomasz; Mahal, Lara K.

In: Journal of Biological Chemistry, Vol. 291, No. 3, 15.01.2016, p. 1529-37.

Research output: Contribution to journalArticle

@article{2a73432fd3854dd498fbbef09c53f927,
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.",
author = "Vaiana, {Christopher A} and Tomasz Kurcon and Mahal, {Lara K}",
note = "{\circledC} 2016 by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2016",
month = "1",
day = "15",
doi = "10.1074/jbc.M115.672220",
language = "English (US)",
volume = "291",
pages = "1529--37",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression

AU - Vaiana, Christopher A

AU - Kurcon, Tomasz

AU - Mahal, Lara K

N1 - © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2016/1/15

Y1 - 2016/1/15

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M115.672220

DO - 10.1074/jbc.M115.672220

M3 - Article

VL - 291

SP - 1529

EP - 1537

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -