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Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Journal of Biomedical Research 2024年第4期38卷 348-357页

作者： Mengfan Guo Jingyuan Liu Yujuan Zhang Jingjing Gu Junyi Xin Mulong Du Haiyan Chu Meilin Wang Hanting Liu Zhengdong Zhang Departments of Environmental Genomics and Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthJiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public Health/Institute of Clinical Researchthe Affiliated Taizhou People's Hospital of Nanjing Medical UniversityNanjing Medical UniversityNanjingJiangsu 211166China Departments of Environmental Genomics and Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthJiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjingJiangsu 211166China Department of Biostatistics Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer *** using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and *** results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

关键词： o-glycosylation genetic variants immune status gastric cancer

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Emerging roles of podoplanin in vascular development and homeostasis

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Frontiers of Medicine 2015年第4期9卷 421-430页

作者： Yanfang Pan Lijun Xia Department of Non-Communicable Diseases Control and Prevention Zhejiang Provincial Center for Disease Control and Prevention Hangzhou 310051 China State Key Laboratory of Bio-organic and Natural Products Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai 200032 China Cardiovascular Biology Research Program Oklahoma Medical Research Foundation OK 73104 USA

Podoplanin （PDPN） is a mucin-type o-glycoprotein expressed in diverse cell types, such as lymphatic endothelial cells （LECs） in the vascular system and fibroblastic reticular cells （FRCs） in lymph nodes. PDPN on LECs or FRCs activates CLEC-2 in platelets, triggering platelet activation and/or aggregation through downstream signaling events, including activation of Syk kinase. This mechanism is required to initiate and maintain separation of blood and lymphatic vessels and to stabilize high endothelial venule integrity within lymph nodes. In the vascular system, normal expression of PDPN at the LEC surface requires transcriptional activation of Pdpn by Proxl and modification of PDPN with core 1-derived o-glycans. This review provides a comprehensive overview of the roles of PDPN in vascular development and lymphoid organ maintenance and discusses the mechanisms that regulate PDPN expression related to its function.

关键词： podoplanin CLEC-2 Proxl o-glycosylation lymphatic vascular development and maintenance lymphoid organ homeostasis

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GalNAc-T4 putatively modulates the estrogen regulatory network through FoXA1 glycosylation in human breast cancer cells

GalNAc-T4 putatively modulates the estrogen regulatory netwo...

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第五届泛环渤海生物化学与分子生物学会学术交流会

作者： Bachir Niang Xixi Chen Liyuan Jin Qiong Wu Cheng Zhang Yi Han Jianing Zhang Department of Biochemistry Institute of GlycobiologyDalian Medical University School of Life Science and Medicine Dalian University of Technology

GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of Gal NAc to Serine or Threonine residues in the initial step of mucin-type o-linked protein glycosylation. This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. Most of the breast cancer subtypes are estrogen receptor positive. Hence the estrogen pathway represents a key regulatory network. We investigated the expression of Gal NAc-T4 in a panel of mammary epithelial cell lines and found its positive correlation to the estrogen status of the cells. FoXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to ERα, but all the aspects of this regulatory mechanism are not fully explored. This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of Estrogen Receptor ERα, FoXA1 and Cyclin D1. Further, our immunoprecipitation assays depicted the possibility of FoXA1 to undergo o-Gal NAc modifications with a decrease of Gal NAc residues in the GALNT4 knockdown cells, and impairment in the FoXA1-ERα association. Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FoXA1. Together these findings suggest a key role for Gal Nac-T4 in the estrogen pathway through FoXA1 glycosylation.

关键词： GALNT4 o-glycosylation ERα FoXA1 VVL

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Synthesis of Vildagliptin-β-<i>o</i>-Glucuronide

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Advances in Chemical Engineering and Science 2012年第3期2卷 379-383页

作者： Yansong Jack Lu Yugang Liu Mahavir Prashad Wen-Chung Shieh Chemical and Analytical Development Novartis Pharmaceuticals Corporation One Health Plaza East Hanover USA

A linear 7-step synthesis of vildagliptin-β-o-glucuronide (2) starting from commercially available D-glucurono-6, 3-lactone (3) was herein achieved with 11.3% overall yield. Efficient preparation of compound 6 in pure α form was obtained, which was proved critical to achieve high anomeric selectivity in β-o-glycosylation later. The direct β-o-glycosylation of vildagliptin (1) containing both a tertiary alcohol and a secondary amine was studied and achieved in good yield. The deprotection step to afford product was delicately executed to avoid hydrolysis of nitrile group. The target compound 2 was obtained after purification by reversed-phase C18 chromatography.

关键词： Vildagliptin o-glycosylation DPP-4 Inhibitors Type-2 Diabetes

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FeCl3/C:a Highly Efficient and Reusable Catalyst in Glycochemistry

FeCl3/C:a Highly Efficient and Reusable Catalyst in Glycoche...

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中国化学会第三届全国糖化学会议

作者： Jiafen Zhou Xuan Chen Wenshuai Si Heshan Chen Juan Li Xiaosheng Luo Jianbo Zhang School of Chemistry and Molecular Engineering East China Normal University

Various catalysts,especially metallic catalysts have been thoroughly investigated to achieve different transformations in *** this progress,it is still desirable to find mild,inexpensive,and recyclable catalysts for carbohydrate *** our ongoing efforts to prepare oligosaccharide mimics for the development of carbohydrate-based drugs,in which we often required protected sugars or glycosides as basic ***,with the increase of environment consciousness of human beings,many chemists have explored lots of metal-free catalysts in order to replace liquid *** the organic and engineering section,solid acids are coming to the *** acids have participated in the many reactions of *** these solid acids,FeCl3/C is a novel *** is not only easy to prepare and preserve,but also convenient to remove and is nonpoisonous and *** this research,we have applied FeCl/C as an efficient and recyclable catalyst to synthesize sugar peracetate,2,3-unsaturated glycosides and alkyl *** catalyst has the advantages of being inexpensive,catalyzing rapid reactions,affording high yields,and having simple workup *** expected that this catalyst would find more applications in carbohydrate synthesis.

关键词： Iron o-glycosylation 2,3-dideoxy glycosides

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Development and application of a novelmicroarray construction method for Mucin-type o-glycans

Development and application of a novelmicroarray constructio...

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2020年糖科学青年科技论坛

作者： Lijing Nan Xiangdong Xue Jiao Li Cheng Li Mengjun Tang Ying Zhang College of Life Sciences Northwest University

Mucin-type o-glycans（MoGs） are widely distributed at the membrane of cells（especially gastric mucosal cells） at a high-abundance expression *** are the pivotal molecules in the induction of cell signal transduction and infection of helicobacter pylori to host,which in turn leads to the development of several diseases such as gastroenteritis,ulcers and stomach ***,the recognition and binding interaction between glycans and its receptor is the precondition for its ***,systematic screening of MoGs that play roles in the bacterial infection would be of great importance for screening the novel disease prevention and cure *** microarray is an indispensable tool to screen the interaction between glycans and their *** to structural complexity and the lack of methods for releasing MoGs,few methods are available for the construction of o-glycan ***,we have a longstanding interest in developing novel methods for construction of MoG *** employ an p-ethynylbenzyl-2-acetamido-3,4,6-tri-o-acetyl-2-deoxy-a-D-galactopyranoside that could be used by gastric mucosal cell line GES-1 to amplify the MoGs with p-ethynylbenzyl group,which not only allows the HPLC separation to prepare the single o-glycan,but also facilitates the conjugation of single o-glycan with p-ethynylbenzyl group to azide modified slide through click chemistry,enabling the establishment of a novel and efficient strategy for construction of MoG ***,we would utilize the strengths of Mucin-type o-glycan microarray in high-throughput profiling of interaction between glycans and their receptors,to provide an effective and powerful approach needed in elucidating the structure bases of MoGs in the infection procedure of helicobacter pylori to host systematically,which is of great importance in designing and synthesizing the potential chemical against the infection of helicobacter pylori to *** would also afford a novel powerful plat

关键词： o-glycosylation aryl-α-o-glycosides α-o-glycosidation ferric chloride

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Intact o-glycopeptide of haptoglobin in hepatocellular carcinoma

Intact O-glycopeptide of haptoglobin in hepatocellular carci...

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2020年糖科学青年科技论坛

作者： Hong Shu Lei Zhang Yiwei Chen Yijie Guo Limin Li Xinyi Cao Zhao Cao Guoquan Yan Chunlai Lu Chao Liu Shu Zhang Liver Cancer Institute Zhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer InvasionMinistry of Education Department of Clinical Laboratory Cancer Hospital of Guangxi Medical University Institutes of Biomedical Sciences Fudan University Department of Thoracic Surgery Zhongshan HospitalFudan University Beijing Advanced Innovation Center for Precision Medicine Beihang University Department of Clinical Laboratory First Affiliated Hospital of Guangxi Medical University

Haptoglobin(Hp) is one of the acute-phase response proteins secreted by the liver [1] and its aberrant N-glycosylation was previously reported in hepatocellular carcinoma(HCC)[2].In this study,we aimed to discover and confirm its o-glycosylation in liver diseases based on lectin binding and mass spectrometry(MS) ***,serum Hp was purified from patients with liver cirrhosis(LC) and HCC,***,five lectins with o-glycosylation specificity were chosen and lectin blot analysis showed that Hp in HCC bound to these lectins much stronger than that in ***,label-free quantification for intact o-glycopeptides of Hp was *** intact o-glycopeptides were identified on Hp and most of them were elevated in HCC as compared to *** them,the intensity of HYEGSTVEPKK(H1N1S1)corresponding to the glycopeptide of the Hp β chain was the highest in HCC *** o-glycosylation alteration was confirmed using MS quantification method based on o/o C-terminal labelling [3][4].Few studies on Hp o-glycosylation have been previously reported and our study may provide a comprehensive understanding of the glycosylation of Hp in HCC.

关键词： Haptoglobin o-glycosylation Mass spectrometry Lectin Hepatocellular carcinoma

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A facile and one-step direct o-glycosidation method for the stereo-control synthesis of benzyl-α-o-glycosides

A facile and one-step direct O-glycosidation method for the ...

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中国化学会第三届全国糖化学会议

作者： Lijing Nan Xiangdong Xue Jiao Li Mengjun Tang Ying Zhang College of Life Sciences Northwest University

A facile and efficient o-glycosidation method for stereoselective synthesis of benzyl-α-o-glycosides has been *** monosaccharides acetates were chosen as the glycosyl donor to directly glycosidate with benzyl alcohol and its analogues to afford the alkyl-α-oglycosides with desirable stereoselectivity catalyzed by ferric chloride（FeCl3） in stereo-control solvent,1,2-dichloroethane（DCE）.The established method illustrates the advantages like reaction simplicity,desirable α-stereoselectivity,low cost and a wide application scope for the synthesis of several alkyl-α-o-glycosides in good yields（66-93%）,which will make significant contribution to glycochemistry and glycoscience in general.

关键词： o-glycosylation aryl-α-o-glycosides α-o-glycosidation ferric chloride

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