title: MECP2 promotes the growth of gastric cancer cells by suppressing miR-338-mediated antiproliferative effect.
abstract: The methyl-CpG-binding protein 2 (MECP2), a transcriptional suppressor, is involved in gene regulation by binding to methylated promoters. We found that MECP2 is overexpressed in gastric cancer (GC), and that Mecp2 knockdown affects the growth of GC cells both in vitro and in vivo. MECP2 can directly bind to the methylated-CpG island of miR-338 promoter and suppress the expression of two mature microRNAs, namely, miR-338-3p and miR-338-5p. Furthermore, miR-338-5p can suppress GC cell growth by targeting BMI1 (B lymphoma Mo-MLV insertion region 1 homolog). We additionally found that decreased miR-338-5p expression in GC tissues, relative to normal tissues, was significantly negatively correlated with increased BMI1 expression. Silencing MECP2 can indirectly lead to reduced expression of P-REX2, which has been identified as the miR-338-3p target, as well as BMI1 and increasing expression of P16 or P21 both in vitro and in vivo. Altogether, our results indicate that MECP2 promote the proliferation of GC cells via miR-338 (miR-338-3p and miR-338-5p)-mediated antitumor and gene regulatory effect.
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. 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, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. 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, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. China.|Department of Periodontology, Stomatology Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, P. R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Cai
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of pathology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Su'e
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Shaanxi, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. 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, Shaanxi, P. R. China.|Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Shaanxi, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C069077:BMI1 protein, human; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C497392:MECP2 protein, human; C532050:MIRN338 microRNA, human; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; C490712:PREX2 protein, human; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1
keywords: BMI1; MECP2; gastric cancer; miR-338; proliferation