Promoters of Human Cosmc and T-synthase Genes Are Similar in Structure, Yet Different in Epigenetic Regulation

Zeng, Junwei; Mi, Ruifa; Wang, Yingchun; Li, Yujing; Li, Lin; Yao, Bing; Song, Lu; Die, Irma van; Chapman, Arlene B.; Cummings, Richard D.; Jin, Peng; Ju, Tongzhong

doi:10.1074/jbc.m115.654244

Cited by 19 publications

(22 citation statements)

References 73 publications

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“…Moreover, suppression of Cosmc at the transcriptional level has been detected in human cancers, and its elevated expression exerts an inhibitory effect on tumor growth by repressing the expression of the Tn and STn antigens. 29 The Tn and STn antigens belong to the tumor-associated carbohydrate antigens capable of controlling the interaction among carbohydrates. 30 Overexpression of the Tn antigen has been detected in breast cancer tissues, which is correlated with a poor prognosis for overall survival and progression-free survival of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens</p>

Wang

Cui

et al. 2020

CMAR

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These authors contributed equally to this workBackground: Aberrant gene methylation in breast cancer is associated with an unfavorable prognosis. Besides, abnormal Cosmc can induce the expression of Tn and STn antigens. The present study aimed to investigate the roles of Cosmc promoter methylation in breast cancer through the regulation of Tn and STn antigens. Methods: The expression patterns of Cosmc and the Tn and STn antigens in breast cancer cell lines were determined. Cosmc was overexpressed to explore the effects of Cosmc on cell behavior, including the growth, migration, invasion, and apoptosis of breast cancer cells and tumor growth with in vitro and in vivo experiments. Afterwards, a methyltransferase and a methyltransferase inhibitor were used to alter the methylation status of Cosmc to explore the mechanisms related to Cosmc promoter methylation. Results: Cosmc was poorly expressed in breast cancer cells. Cosmc overexpression inhibited cell growth, migration, and invasion while promoting apoptosis in breast cancer cells in vitro and restraining tumor growth in vivo. Cosmc promoter methylation was found to decrease the levels of Cosmc and increased the expression of the Tn and STn antigens in breast cancer. Conclusion: In conclusion, the demethylation of Cosmc mitigates breast cancer progression through the repression of the Tn and STn antigens, which provides evidence for therapeutic considerations for a novel target against breast cancer.

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Section: Discussionmentioning

confidence: 99%

<p>Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens</p>

Wang

Cui

et al. 2020

CMAR

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“…Enzymatic activity was reduced when the transcription factor, SP1/3, binding sites were mutated, suggesting regulation by this transcription factor. In addition, methylome analysis predicted hypermethylation of cosmc promoter region in Tn4 cells, where this gene is silenced, which suggests epigenetic regulation of COSMC but not T-synthase [34].…”

Section: Biological Function Of Tf-antigenmentioning

confidence: 98%

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

Gupta

Leon

Rauth

et al. 2020

Cells

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Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is directed by different glycosyltransferases, depending on the cell in which it is expressed. These small carbohydrate molecules consist of multiple glycan families that facilitate cell–cell interactions, protein interactions, and downstream signaling. An alteration of several types of O-glycan core structures have been implicated in multiple cancers, largely due to differential glycosyltransferase expression or activity. Consequently, aberrant O-linked glycosylation has been extensively demonstrated to affect biological function and protein integrity that directly result in cancer growth and progression of several diseases. Herein, we provide a comprehensive review of several initiating enzymes involved in the synthesis of O-linked glycosylation that significantly contribute to a number of different cancers.

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“…, which lies at a predicted SOX2-OCT4 site 32,33 and rs758263, which lies within the core promoter region for C1GALT1 and is predicted to affect binding of RUNX3, a transcription factor present in B cells that is necessary for class switching to IgA production 34,35 . These in silico predictions coupled with previous in vitro data demonstrating modulation of IgA1 O-galactosylation by Th2 cytokines and IL-6 36,37 , as well as our previous observation that IgA1 O-galactosylation varies depending on the site of antigen encounter and B cell activation 38 , are consistent with an effect of the H1 haplotype on transcriptional control of C1GALT1 particularly in IgA1-committed B cells.…”

Section: Discussionmentioning

confidence: 99%

Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1

Gale

Molyneux

Wimbury

et al. 2017

JASN

105

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IgA nephropathy (IgAN), an important cause of kidney failure, is characterized by glomerular IgA deposition and is associated with changes in O-glycosylation of the IgA1 molecule. Here, we sought to identify genetic factors contributing to levels of galactose-deficient IgA1 (Gd-IgA1) in Caucasian and Chinese populations.Gd-IgA1 levels were elevated in IgAN patients compared with ethnically matched healthy subjects and correlated with evidence of disease progression. Caucasian IgAN patients exhibited significantly higher Gd-IgA1 levels than Chinese patients. Among individuals without IgAN, Gd-IgA1 levels were not correlated with kidney function. Gd-IgA1 level heritability (h ). This association was replicated in GWAS of separate cohorts comprising: 308 UK patients with membranous glomerulonephritis (p<10

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Promoters of Human Cosmc and T-synthase Genes Are Similar in Structure, Yet Different in Epigenetic Regulation

Cited by 19 publications

References 73 publications

<p>Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens</p>

<p>Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens</p>

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1

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