The role of O-glycosylation in human disease

Magalhães, Ana; Duarte, Hugo; Reis, Celso A.

doi:10.1016/j.mam.2021.100964

Cited by 74 publications

(45 citation statements)

References 150 publications

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“…Glycosylation is an important posttranslational modification involving N-glycosylation ( 35 ) and O-glycosylation ( 36 ) and is significantly related to a variety of pathological and physiological processes. Previous studies have found that N-glycosylation is associated with the function of many ion channels, and an association between the dysfunction of glycosylation in potassium channels and long QT syndrome was observed ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

Zheng

Chen

Liu

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThe immune system significantly participates in the pathologic process of atrial fibrillation (AF). However, the molecular mechanisms underlying this participation are not completely explained. The current research aimed to identify critical genes and immune cells that participate in the pathologic process of AF.MethodsCIBERSORT was utilized to reveal the immune cell infiltration pattern in AF patients. Meanwhile, weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules that were significantly correlated with AF. The characteristic genes correlated with AF were identified by the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithm.ResultsIn comparison to sinus rhythm (SR) individuals, we observed that fewer activated mast cells and regulatory T cells (Tregs), as well as more gamma delta T cells, resting mast cells, and M2 macrophages, were infiltrated in AF patients. Three significant modules (pink, red, and magenta) were identified to be significantly associated with AF. Gene enrichment analysis showed that all 717 genes were associated with immunity- or inflammation-related pathways and biological processes. Four hub genes (GALNT16, HTR2B, BEX2, and RAB8A) were revealed to be significantly correlated with AF by the SVM-RFE algorithm and LASSO logistic regression. qRT–PCR results suggested that compared to the SR subjects, AF patients exhibited significantly reduced BEX2 and GALNT16 expression, as well as dramatically elevated HTR2B expression. The AUC measurement showed that the diagnostic efficiency of BEX2, HTR2B, and GALNT16 in the training set was 0.836, 0.883, and 0.893, respectively, and 0.858, 0.861, and 0.915, respectively, in the validation set.ConclusionsThree novel genes, BEX2, HTR2B, and GALNT16, were identified by WGCNA combined with machine learning, which provides potential new therapeutic targets for the early diagnosis and prevention of AF.

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Section: Discussionmentioning

confidence: 99%

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

Zheng

Chen

Liu

et al. 2022

Front. Cardiovasc. Med.

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“…Many glycoproteins have both N-linked sugar chains and O-linked sugar chains ( 168 ). The O-linked glycosylation is carried out in the Golgi apparatus; usually, the first linked sugar unit is N-acetylgalactose, and the linked sites are the hydroxyl groups of Ser, Thr, and Hyp, and then the sugar groups are successively transferred to it to form an oligosaccharide chain; the donor of sugar is also a nucleoside sugar, such as UDP-galactose ( 169 ). As a result of glycosylation, different proteins are marked differently, changing the polypeptide's conformation and increasing the protein's stability ( 170 ).…”

Section: Epigenetic In Tumor Progression and Metastasismentioning

confidence: 99%

Epigenetic modification regulates tumor progression and metastasis through EMT (Review)

et al. 2022

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Epigenetics is the study of heritable molecular determinants that are independent of phenotypic features. The epigenetic features include DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling. In multicellular organisms, the epigenetic state of a cell is critical in determining its differentiation status and its ability to perform its proper function. These processes are now well recognized as being a substantial factor in tumor progression and metastasis. The process through which epithelial cells acquire mesenchymal features is known as epithelial-mesenchymal transition (EMT). EMT is associated with tumorigenesis, invasion, metastasis, and resistance to therapy in cancer. In the present review, we examine the recent studies that demonstrate the biological role of epigenetics, in particular, DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling in tumor progression and metastasis by regulating EMT status, and we provide an overview of the current state of knowledge regarding the epigenetics involvement in tumor progression and metastasis. Because epigenetic changes can be reversed, learning more about their biological roles in EMT will not only help us better understand how cancer progresses and spreads, but it will also help us identify new ways to diagnose and treat human malignancy which is currently lacking in the clinical setting.

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“…The O-glycosylation process refers to the addition of N-acetylgalactosamine (GalNAc) to serine or threonine residues in proteins and the addition of other sugar branches to create more complex structures ( 56 , 57 ). The biosynthesis of O-glycans is controlled by T-synthase (C1GalT1) ( 58 , 59 ).…”

Section: Cd44 O-glycosylation Regulates the Aggressiveness Of Cancermentioning

confidence: 99%

CD44 Glycosylation as a Therapeutic Target in Oncology

Liao

Wang

et al. 2022

Front. Oncol.

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The interaction of non-kinase transmembrane glycoprotein CD44 with ligands including hyaluronic acid (HA) is closely related to the occurrence and development of tumors. Changes in CD44 glycosylation can regulate its binding to HA, Siglec-15, fibronectin, TM4SF5, PRG4, FGF2, collagen and podoplanin and activate or inhibit c-Src/STAT3/Twist1/Bmi1, PI3K/AKT/mTOR, ERK/NF-κB/NANOG and other signaling pathways, thereby having a profound impact on the tumor microenvironment and tumor cell fate. However, the glycosylation of CD44 is complex and largely unknown, and the current understanding of how CD44 glycosylation affects tumors is limited. These issues must be addressed before targeted CD44 glycosylation can be applied to treat human cancers.

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The role of O-glycosylation in human disease

Cited by 74 publications

References 150 publications

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

Epigenetic modification regulates tumor progression and metastasis through EMT (Review)

CD44 Glycosylation as a Therapeutic Target in Oncology

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