The Roles of O-GlcNAc Cycling Enzymes in Lung Cancer Progression
博士 === 國立陽明大學 === 生化暨分子生物研究所 === 106 === Protein O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a highly dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on a wide variety of nuclear and cytoplasmic p...
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ndltd-TW-106YM0051070282019-09-12T03:37:44Z http://ndltd.ncl.edu.tw/handle/k6b3kt The Roles of O-GlcNAc Cycling Enzymes in Lung Cancer Progression 探討氧連結N-乙醯葡萄糖胺修飾酵素在肺癌進程中的角色 Chia-Hung Lin 林家弘 博士 國立陽明大學 生化暨分子生物研究所 106 Protein O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a highly dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on a wide variety of nuclear and cytoplasmic proteins. Two O-GlcNAc cycling enzymes modulate cellular O-GlcNAcylation: O-GlcNAc transferase (OGT) catalyzes the transfer of GlcNAc from UDP-GlcNAc, while O-GlcNAcase (OGA) catalyzes the removal of O-GlcNAc. Proteins with O-GlcNAcylation are involved in many crucial biological functions, including transcriptional regulation, signal transduction, metabolism, cell cycle control and epigenetics mechanisms. Therefore, dysregulation of O-GlcNAcylation may contribute to the pathogenesis of many diseases, including diabetes, neurodegenerative diseases, and cancer. Cancer cells exhibit altered metabolism characterized by increased glucose and glutamine uptake which may result in elevated cellular O-GlcNAc levels. Although studies have shown that OGT expression and O-GlcNAcylation are up-regulated in various human malignancies, it still remains elusive how O-GlcNAc cycling enzymes and O-GlcNAcylation participate in the pathogenic mechanisms of cancer. The objective of this thesis research aims at understanding the roles of O-GlcNAc cycling enzymes and O-GlcNAcylation in lung cancer progression. The main findings are: (i) The level of OGT protein in the tumor may serve as a prognostic biomarker for predicting poor survival in patients with early-stage lung adenocarcinoma; (ii) Differentially expressed O-GlcNAcylated proteins which are associated with lung cancer aggressiveness have been identified; and (iii) The homeostasis of O-GlcNAcylation in lung cancer cells is maintained by feedback regulation of O-GlcNAc cycling enzymes. Together, these results provide further insight into the functional significance of O-GlcNAcylation in lung cancer progression. Mei-Yu Chen 陳美瑜 2018 學位論文 ; thesis 132 en_US |
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博士 === 國立陽明大學 === 生化暨分子生物研究所 === 106 === Protein O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a highly dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on a wide variety of nuclear and cytoplasmic proteins. Two O-GlcNAc cycling enzymes modulate cellular O-GlcNAcylation: O-GlcNAc transferase (OGT) catalyzes the transfer of GlcNAc from UDP-GlcNAc, while O-GlcNAcase (OGA) catalyzes the removal of O-GlcNAc. Proteins with O-GlcNAcylation are involved in many crucial biological functions, including transcriptional regulation, signal transduction, metabolism, cell cycle control and epigenetics mechanisms. Therefore, dysregulation of O-GlcNAcylation may contribute to the pathogenesis of many diseases, including diabetes, neurodegenerative diseases, and cancer. Cancer cells exhibit altered metabolism characterized by increased glucose and glutamine uptake which may result in elevated cellular O-GlcNAc levels. Although studies have shown that OGT expression and O-GlcNAcylation are up-regulated in various human malignancies, it still remains elusive how O-GlcNAc cycling enzymes and O-GlcNAcylation participate in the pathogenic mechanisms of cancer. The objective of this thesis research aims at understanding the roles of O-GlcNAc cycling enzymes and O-GlcNAcylation in lung cancer progression. The main findings are: (i) The level of OGT protein in the tumor may serve as a prognostic biomarker for predicting poor survival in patients with early-stage lung adenocarcinoma; (ii) Differentially expressed O-GlcNAcylated proteins which are associated with lung cancer aggressiveness have been identified; and (iii) The homeostasis of O-GlcNAcylation in lung cancer cells is maintained by feedback regulation of O-GlcNAc cycling enzymes. Together, these results provide further insight into the functional significance of O-GlcNAcylation in lung cancer progression.
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author2 |
Mei-Yu Chen |
author_facet |
Mei-Yu Chen Chia-Hung Lin 林家弘 |
author |
Chia-Hung Lin 林家弘 |
spellingShingle |
Chia-Hung Lin 林家弘 The Roles of O-GlcNAc Cycling Enzymes in Lung Cancer Progression |
author_sort |
Chia-Hung Lin |
title |
The Roles of O-GlcNAc Cycling Enzymes in Lung Cancer Progression |
title_short |
The Roles of O-GlcNAc Cycling Enzymes in Lung Cancer Progression |
title_full |
The Roles of O-GlcNAc Cycling Enzymes in Lung Cancer Progression |
title_fullStr |
The Roles of O-GlcNAc Cycling Enzymes in Lung Cancer Progression |
title_full_unstemmed |
The Roles of O-GlcNAc Cycling Enzymes in Lung Cancer Progression |
title_sort |
roles of o-glcnac cycling enzymes in lung cancer progression |
publishDate |
2018 |
url |
http://ndltd.ncl.edu.tw/handle/k6b3kt |
work_keys_str_mv |
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