title: Silencing β-linked N-acetylglucosamine transferase induces apoptosis in human gastric cancer cells through PUMA and caspase-3 pathways.
abstract: β-linked N-acetylglucosamine (GlcNAc) is a monosaccharide that is catalyzed by O-GlcNAcylation transferase (OGT) to bind serine or threonine hydroxyl moieties of numerous nuclear and cytoplasmic proteins. Recent studies have shown that O-GlcNAcylation is elevated in various cancer types, which is associated with oncogenesis and tumor progression. However, whether OGT is expressed and/or plays a role in gastric cancer is unknown. In the present study, we used qPCR to determine that OGT mRNA levels are significantly elevated in gastric cancer tissues compared with that in corresponding adjacent tissues. In addition, in vivo silencing of OGT in nude mice suppressed tumor proliferation and decreased tumor burden. Furthermore, in vitro OGT knockdown induced more cell apoptosis through increasing PUMA and caspase-3 expression. We used a glycan-binding protein gene microarray to identify potential downstream target genes of OGT, and found that apoptosis-related genes such as galectin and HBEGF were decreased after OGT suppression, suggesting that OGT silencing induces apoptosis in gastric cancer tissues. We concluded that OGT plays a key role in gastric cancer proliferation and survival, and could be a potential target for therapy.
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ti
authors.initials: T
authors.lastname: Wen
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Kezuo
authors.initials: K
authors.lastname: Hou
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Beilin, Xi'an, Shaanxi 710069, P.R. China.
authors.forename: Hanjie
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Yangguang
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D053148:Caspase 3