title: MeCP2 Promotes Gastric Cancer Progression Through Regulating FOXF1/Wnt5a/β-Catenin and MYOD1/Caspase-3 Signaling Pathways.
abstract: Methyl-CpG binding protein 2 (MeCP2) has recently been characterized as an oncogene frequently amplified in several types of cancer. However, its precise role in gastric cancer (GC) and the molecular mechanism of MeCP2 regulation are still largely unknown. Here we report that MeCP2 is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic features of GC. In our experiments, knockdown of MeCP2 inhibited tumor growth. Molecular mechanism of MeCP2 regulation was investigated using an integrated approach with combination of microarray analysis and chromatin immunoprecipitation sequencing (ChIP-Seq). The results suggest that MeCP2 binds to the methylated CpG islands of FOXF1 and MYOD1 promoters and inhibits their expression at the transcription level. Furthermore, we show that MeCP2 promotes GC cell proliferation via FOXF1-mediated Wnt5a/β-Catenin signaling pathway and suppresses apoptosis through MYOD1-mediated Caspase-3 signaling pathway. Due to its high expression level in GC and its critical function in driving GC progression, MeCP2 represents a promising therapeutic target for GC treatment.
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Shaanxi, Xi'an 710061, People's Republic of 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, Shaanxi, Xi'an 710061, People's Republic of 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, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Tong
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of 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, Shaanxi, Xi'an 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Oncology Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Du
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Shaanxi, Xi'an 710061, People's Republic of 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, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Ni
authors.initials: N
authors.lastname: Hou
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Xiaoge
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Lumin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China.
authors.forename: Yanke
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, Xi'an 710061, People's Republic of China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Shaanxi, Xi'an 710061, People's Republic of China. Electronic address: hchen@xjtu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D000071818:Wnt-5a Protein / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein; D051176:beta Catenin; D053148:Caspase 3
keywords: Caspase-3; FOXF1; Gastric cancer; MYOD1; MeCP2; Wnt5a