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MiRNA proxy approach reveals hidden functions of glycosylation.

ABSTRACT: Glycosylation, the most abundant posttranslational modification, holds an unprecedented capacity for altering biological function. Our ability to harness glycosylation as a means to control biological systems is hampered by our inability to pinpoint the specific glycans and corresponding biosynthetic enzymes underlying a biological process. Herein we identify glycosylation enzymes acting as regulatory elements within a pathway using microRNA (miRNA) as a proxy. Leveraging the target network of the miRNA-200 family (miR-200f), regulators of epithelial-to-mesenchymal transition (EMT), we pinpoint genes encoding multiple promesenchymal glycosylation enzymes (glycogenes). We focus on three enzymes, beta-1,3-glucosyltransferase (B3GLCT), beta-galactoside alpha-2,3-sialyltransferase 5 (ST3GAL5), and (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5), encoding glycans that are difficult to analyze by traditional methods. Silencing these glycogenes phenocopied the effect of miR-200f, inducing mesenchymal-to-epithelial transition. In addition, all three are up-regulated in TGF-?-induced EMT, suggesting tight integration within the EMT-signaling network. Our work indicates that miRNA can act as a relatively simple proxy to decrypt which glycogenes, including those encoding difficult-to-analyze structures (e.g., proteoglycans, glycolipids), are functionally important in a biological pathway, setting the stage for the rapid identification of glycosylation enzymes driving disease states.

SUBMITTER: Kurcon T

PROVIDER: S-EPMC4466752 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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miRNA proxy approach reveals hidden functions of glycosylation.

Kurcon Tomasz T Liu Zhongyin Z Paradkar Anika V AV Vaiana Christopher A CA Koppolu Sujeethraj S Agrawal Praveen P Mahal Lara K LK

Proceedings of the National Academy of Sciences of the United States of America 20150526 23

Glycosylation, the most abundant posttranslational modification, holds an unprecedented capacity for altering biological function. Our ability to harness glycosylation as a means to control biological systems is hampered by our inability to pinpoint the specific glycans and corresponding biosynthetic enzymes underlying a biological process. Herein we identify glycosylation enzymes acting as regulatory elements within a pathway using microRNA (miRNA) as a proxy. Leveraging the target network of t ...[more]

PMID: 26015571

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Project description:PurposeCommonly-used violence surveillance systems are biased towards certain populations due to overreporting or over-scrutinized. Hospital discharge data may offer a more representative view of violence, through use of proxy codes, i.e. diagnosis of injuries correlated with violence. The goals of this paper are to compare the trends in violence in Minnesota, and associations of county-level demographic characteristics with violence rates, measured through explicitly diagnosed violence and proxy codes. It is an exploration of how certain sub-populations are overrepresented in traditional surveillance systems.MethodsUsing Minnesota hospital discharge data linked with census data from 2004 to 2014, this study examined the distribution and time trends of explicit, proxy, and combined (proxy and explicit) codes for child abuse, intimate partner violence (IPV), and elder abuse. The associations between county-level risk factors (e.g., poverty) and county violence rates were estimated using negative binomial regression models with generalized estimation equations to account for clustering over time.ResultsThe main finding was that the patterns of county-level violence differed depending on whether one used explicit or proxy codes. In particular, explicit codes suggested that child abuse and IPV trends were flat or decreased slightly from 2004 to 2014, while proxy codes suggested the opposite. Elder abuse increased during this timeframe for both explicit and proxy codes, but more dramatically when using proxy codes. In regard to the associations between county level characteristics and each violence subtype, previously identified county-level risk factors were more strongly related to explicitly-identified violence than to proxy-identified violence. Given the larger number of proxy-identified cases as compared with explicit-identified violence cases, the trends and associations of combined codes align more closely with proxy codes, especially for elder abuse and IPV.ConclusionsViolence surveillance utilizing hospital discharge data, and particularly proxy codes, may add important information that traditional surveillance misses. Most importantly, explicit and proxy codes indicate different associations with county sociodemographic characteristics. Future research should examine hospital discharge data for violence identification to validate proxy codes that can be utilized to help to identify the hidden burden of violence.

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MiRNA proxy approach reveals hidden functions of glycosylation.

Publications

miRNA proxy approach reveals hidden functions of glycosylation.

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