4.7 Article

Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function

期刊

BIOMEDICINES
卷 10, 期 8, 页码 -

出版社

MDPI
DOI: 10.3390/biomedicines10081805

关键词

glycosylation machinery; genomics; transcriptomics; healthy tissues; cancer

资金

  1. Fundacao para a Ciencia e Tecnologia (FCT) [UIDP/04378/2020, UIDB/04378/2020, PTDC/MED-ONC/28660/2017, CEECIND/02699/2017, SFRH/BD/124326/2016]
  2. Associate Laboratory Institute for Health and Bioeconomy-i4HB [LA/P/0140/2020]
  3. European Union [825575, EJPRD/0001/2020]
  4. FEDER [22153-01/SAICT/2016]
  5. Common Fund of the Office of the Director of the National Institutes of Health
  6. NCI
  7. NHGRI
  8. NHLBI
  9. NIDA
  10. NIMH
  11. NINDS
  12. Fundação para a Ciência e a Tecnologia [PTDC/MED-ONC/28660/2017, SFRH/BD/124326/2016, EJPRD/0001/2020] Funding Source: FCT

向作者/读者索取更多资源

This study provides insight into the complex role of glycosylation in humans by combining genome and transcriptome profiles. It reveals that glycosylation factors are tightly regulated in healthy tissues, but impaired in aging and tumorigenesis. They may serve as potential prognostic biomarkers or therapeutic targets.
Glycosylation is a fundamental cellular process affecting human development and health. Complex machinery establishes the glycan structures whose heterogeneity provides greater structural diversity than other post-translational modifications. Although known to present spatial and temporal diversity, the evolution of glycosylation and its role at the tissue-specific level is poorly understood. In this study, we combined genome and transcriptome profiles of healthy and diseased tissues to uncover novel insights into the complex role of glycosylation in humans. We constructed a catalogue of human glycosylation factors, including transferases, hydrolases and other genes directly involved in glycosylation. These were categorized as involved in N-, O- and lipid-linked glycosylation, glypiation, and glycosaminoglycan synthesis. Our data showed that these glycosylation factors constitute an ancient family of genes, where evolutionary constraints suppressed large gene duplications, except for genes involved in O-linked and lipid glycosylation. The transcriptome profiles of 30 healthy human tissues revealed tissue-specific expression patterns preserved across mammals. In addition, clusters of tightly co-expressed genes suggest a glycosylation code underlying tissue identity. Interestingly, several glycosylation factors showed tissue-specific profiles varying with age, suggesting a role in ageing-related disorders. In cancer, our analysis revealed that glycosylation factors are highly perturbed, at the genome and transcriptome levels, with a strong predominance of copy number alterations. Moreover, glycosylation factor dysregulation was associated with distinct cellular compositions of the tumor microenvironment, reinforcing the impact of glycosylation in modulating the immune system. Overall, this work provides genome-wide evidence that the glycosylation machinery is tightly regulated in healthy tissues and impaired in ageing and tumorigenesis, unveiling novel potential roles as prognostic biomarkers or therapeutic targets.

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