High<i>O</i>-linked<i>N</i>-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma

Lin, Yi; Lin, Chia Hung; Yeh, Yi Chen; Ho, Hsiang‐Ling; Wu, Yu Chung; Chen, Mei Yu; Chou, Teh Ying

doi:10.18632/oncotarget.25772

Cited by 17 publications

(29 citation statements)

References 25 publications

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“…With the sparse information, it is unclear whether all cell types utilize conserved mechanisms to regulate the expression of OGA and OGT upon changes of cellular O -GlcNAcylation. We have previously revealed a positive correlation between OGT and OGA protein expression in lung adenocarcinoma tissues [ 20 ]. In this study, we further investigated the regulatory loops involved in adjusting the expression of the two O -GlcNAc-cycling enzymes when changes of cellular O -GlcNAcylation status occur in lung cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

Lin

Liao

Chen

et al. 2021

IJMS

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Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

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Section: Introductionmentioning

confidence: 99%

Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

Lin

Liao

Chen

et al. 2021

IJMS

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“…[12][13][14][15] Recently, several cancer studies have reported that elevated O-GlcNAc is associated with tumorigenesis and cancer cell metastasis. 12,[16][17][18][19][20][21][22][23][24][25] Moreover, several previous studies have shown that hyper-O-GlcNAc and overexpression of OGT were associated with worse clinicopathological outcomes in various cancers. 17,21,26,27 Osteosarcoma is most commonly found in children, adolescents and young adults, accounting for approximately 20% of all primary bone tumors.…”

mentioning

confidence: 99%

Relationship Between O-GlcNAcase Expression and Prognosis of Patients With Osteosarcoma

Sombutthaweesri

Chamusri

et al. 2021

Applied Immunohistochemistry &Amp; Molecular Morphology

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Background: Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modi cation of tumor-associated proteins. However, its implication in the pathogenesis of osteosarcoma remains unclear. This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues and to nd correlations between the levels or expressions and several clinicopathologic parameters.Methods: Immunohistochemistry was conducted in 109 formalin-xed, para n-embedded bone tissue sections that were derived from 109 rst diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). Correlations between the imunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated.Results: A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). Univariate analysis revealed signi cantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was signi cantly associated with shorter overall survival. Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male gender (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were signi cantly correlated with short metastasis-free survival. But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006).Conclusions: O-GlcNAc pathway, especially OGA, involved in pathogenesis and aggressiveness of osteosarcoma. Low level of OGA expression may be used as a poor prognostic indicator. BackgroundO-GlcNAcylation (O-GlcNAc) is a post-translational modi cation of proteins associated with regulation of various protein functions by an addition of N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues of the target proteins. This modi cation is a dynamic and reversible process, strictly regulated by two important enzymes, O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA), which add and remove the GlcNAc moieties, respectively. 1-5 O-GlcNAc is involved in many cellular processes, such as signal transduction, transcription, cell cycle control, and epigenetic control of gene expressions in response to stress and nutrient imbalance. 6,7 In this regard, O-GlcNAc homeostasis needs to be maintained in order to achieve proper cellular functions.Aberrations of O-GlcNAc are associated with the pathogenesis of many human diseases, including diabetes, neurodegenerative diseases and cancers. 6,[8][9][10][11] With respect to cancer pathogenesis and progression, several key players, such as p53, c-Myc, Forkhead box M1 (FoxM1) etc., have been shown to

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“…In many types of cancer such as breast, prostate, lung, colorectal, and esophageal cancers, higher levels of OGT/O-GlcNAcylation are observed (29), suggesting that alterations of the intracellular level of OGT and O-GlcNAcylation are tightly associated with tumorigenesis, which might further participate directly or indirectly in the regulation of the biological processes associated with cancer metastasis. For example, the increased levels of OGT/O-GlcNAcylation in patients with lung cancer or colon cancer are closely correlated with poor overall survival, as well as the anchorage-independent growth, migration, and invasion ability of lung and colon cancer cell lines (22,23,30,31). Elevated OGT proteins, as well as O-GlcNAcylation level, are also found in both breast cancer cells and tumor tissues (24,25).…”

Section: Imbalanced O-glcnacylation In Cancer Cellsmentioning

confidence: 99%

Functional Analysis of O-GlcNAcylation in Cancer Metastasis

Jin

Qiu

et al. 2020

Front. Oncol.

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One common and reversible type of post-translational modification (PTM) is the addition of O-linked b-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), and its dynamic balance is controlled by O-GlcNAc transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA) through the addition or removal of O-GlcNAc groups. A large amount of research data confirms that proteins regulated by O-GlcNAcylation play a pivotal role in cells. In particularly, imbalanced levels of OGT and O-GlcNAcylation have been found in various types of cancers. Recently, increasing evidence shows that imbalanced O-GlcNAcylation directly or indirectly impacts the process of cancer metastasis. This review summarizes the current understanding of the influence of O-GlcNAc-proteins on the regulation of cancer metastasis. It will provide a theoretical basis to further elucidate of the molecular mechanisms underlying cancer emergence and progression.

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HighO-linkedN-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma

Cited by 17 publications

References 25 publications

Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

Relationship Between O-GlcNAcase Expression and Prognosis of Patients With Osteosarcoma

Functional Analysis of O-GlcNAcylation in Cancer Metastasis

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