Insights into miRNA regulation of the human glycome

Kasper, Brian; Koppolu, Sujeethraj; Mahal, Lara K.

doi:10.1016/j.bbrc.2014.01.034

Cited by 32 publications

(41 citation statements)

References 46 publications

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“…Recent work by our laboratory has shown miRNAs are major regulators of the glycome (7–9). To date 10 human glycogenes have been validated as miRNA targets in the literature (7, 8).…”

mentioning

confidence: 99%

miRNA proxy approach reveals hidden functions of glycosylation

Kurćon

Liu

Paradkar

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceCarbohydrates hold an unprecedented capacity for altering biological function, but determining which glycans and underlying enzymes are crucial for a specific biological pathway is a major impediment to our understanding of this posttranslational modification. Here we demonstrate that the mRNA target networks of microRNA (miRNA), small noncoding RNA, identify glycosylation enzymes acting as regulatory elements within a biological pathway. Leveraging the miRNA-200 family (miR-200f), regulators of epithelial-to-mesenchymal transition (EMT), we identify multiple promesenchymal glycosylation enzymes. Silencing miR-200f–targeted glycogenes phenocopies the effect of miR-200f, inducing mesenchymal-to-epithelial transition. These enzymes are upregulated in TGF-β–induced EMT, suggesting tight integration within the signaling network. Our work indicates that miRNA networks can be used to identify crucial glycosylation enzymes driving disease states.

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“…Recent work by our laboratory has shown miRNAs are major regulators of the glycome (7–9). To date 10 human glycogenes have been validated as miRNA targets in the literature (7, 8).…”

mentioning

confidence: 99%

miRNA proxy approach reveals hidden functions of glycosylation

Kurćon

Liu

Paradkar

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Although OGT was not regulated by miR-424 in MCF-7, the miRNA-dependent regulation of OGT is of special interest. Previous analysis of the 3Ј-UTR of OGT revealed that it is one of the most highly regulated glycogenes (41). O-GlcNAc, the epitope controlled by this enzyme, is involved in cell proliferation (42,43), consistent with targeting by miR-424.…”

Section: Discussionmentioning

confidence: 93%

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

Vaiana¹,

Kurćon

Mahal

2016

Journal of Biological Chemistry

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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 ␤ (TGF␤), 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 ␤-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 TGF␤, an inducer of miR-424. Knockdown of MGAT4A induces cell cycle arrest through decreasing CCND1 levels. MGAT4A does not affect levels of ␤-1,6 branched N-glycans, arguing that this effect is specific to ␤-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.

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“…Mahal and co-workers (51) revealed critical nodes in the global glycosylation network accessible to microRNA regulation, providing an miRNA regulatory map for glycogenes both in the N-linked and O-linked glycosylation pathways, among which galnt1, galnt7, fut4, fut8, and manea are predicted to be highly regulated genes. Changes in microRNA may underlie the altered glycosylation observed in dynamic processes in cancer phenotypes (52). Bernardi et al (53) reported that fucosyltransferase 8 (FUT8), catalyzing core fucosylation, was regulated by miR-122 and miR-34a during hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Decreased Expression of Hepatocyte Nuclear Factor 4α (Hnf4α)/MicroRNA-122 (miR-122) Axis in Hepatitis B Virus-associated Hepatocellular Carcinoma Enhances Potential Oncogenic GALNT10 Protein Activity

Liu

et al. 2015

Journal of Biological Chemistry

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Background: GALNT, the initial enzyme in mucin-type O-glycosylation, plays critical roles in cancer etiology. Results: GALNT10-induced cellular proliferation was associated with EGFR activation mediated by down-regulation of miR-122 in HBV-associated HCC. Conclusion: A regulatory pathway of Hnf4␣/miR-122/GALNT10/EGFR may represent a possible mechanism underlying HBV-associated hepatocarcinogenesis. Significance: This finding provides a novel role for O-glycosylation in HCC pathogenesis.

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Insights into miRNA regulation of the human glycome

Cited by 32 publications

References 46 publications

miRNA proxy approach reveals hidden functions of glycosylation

miRNA proxy approach reveals hidden functions of glycosylation

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

Decreased Expression of Hepatocyte Nuclear Factor 4α (Hnf4α)/MicroRNA-122 (miR-122) Axis in Hepatitis B Virus-associated Hepatocellular Carcinoma Enhances Potential Oncogenic GALNT10 Protein Activity

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