title: MeCP2 regulated glycogenes contribute to proliferation and apoptosis of gastric cancer cells.
abstract: Aberrant glycogene and glycan expression is intimately associated with carcinogenesis, invasion, and metastasis of gastric cancer (GC); however the regulatory mechanisms for glycogenes in GC cells remain unclear. Methyl-CpG-binding protein 2 (MeCP2) regulates genes by binding to methylated promoters, and in our previous work we found that it is overexpressed in GC cell lines and tissues, functioning as an oncogene. In this study we detected the expression of 212 glycogenes in MeCP2 silenced GC cells versus control using the Agilent Whole Human Genome Microarray and mining the data through bioinformatic analysis. A total of 10 glycogenes exhibited increased expression (FC ≥ 2, P < 0.05), while 16 showed decreased expression (FC ≤ 2, P < 0.05) in the MeCP2 silenced cells, which corresponded to down-regulation of Lewis antigens (UEA-I), T/Tn antigens (PNA), and mature N-glycans (PHA-E and PHA-E+L) and up-regulation of lactosylceramide, a precursor oligosaccharide of N-glycans. Examination of the TCGA Gastric Cancer databases demonstrated that nine glycogenes (24.6%) were oppositely regulated by MeCP2 in MeCP2 knockdown BGC-823 cells relative to their expression level in GC tissues, and might be downstream genes of MeCP2. Individual gene analysis suggested that neutral alpha-glucosidase AB (GANAB) knockdown can rescue the effects of MeCP2 overexpression on GC cells. MeCP2 promotes GANAB by binding to the second methylated CpG island (206 bp, -12916 to -13122) of the GANAB promoter. In conclusion, glycogenes can be either up- or down-regulated by MeCP2 directly or indirectly to alter the glycopatterning and affect the proliferation and apoptosis of GC cells.
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Tong
authors.affiliation: Department of Biochemistry and Molecular Biology, University of OklahomaHealth Science Center, Oklahoma City, OK, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hoover
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Yingxun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Lumin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
authors.forename: Tusheng
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006003:Glycogen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D051783:Methyl-CpG-Binding Protein 2; D006003:Glycogen
keywords: GANAB; MeCP2; gastric cancer; glycogene