title: microRNA-155 is downregulated in gastric cancer cells and involved in             cell metastasis.
abstract: microRNA-155 (miR-155), an important multifunctional microRNA, has been implicated in the development of multiple solid tumors, yet, its role in gastric cancer cells has not been fully elucidated. In this study, we find that miR-155 was significantly downregulated in gastric cancer cell lines compared with an immortalized gastric epithelial cell line (GES-1). Overexpression of miR-155 in SGC-7901 and MKN-45 gastric cancer cells dramatically suppressed cell migration, invasion and adhesion in vitro. Overexpression of miR-155 significantly reduced the protein levels of SMAD2 and repressed the activity of a luciferase reporter containing one of the two predicted miR-155 binding sites in SMAD2 3'-UTR, indicating that SMAD2 may be a miR-155 target gene. miR-155 expression was also remarkably restored by a DNA demethylating agent (5-Aza-2-deoxycytidine) in SGC-7901 and MKN-45 gastric cancer cells. Taken together, these data suggest that miR-155 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting SMAD2, and its downregulation in gastric cancer cells may be partly ascribed to DNA methylation.
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Nie
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Su
authors.forename: Jian-Fang
authors.initials: JF
authors.lastname: Li
authors.forename: Ying-Yan
authors.initials: YY
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.forename: Qin-Long
authors.initials: QL
authors.lastname: Qu
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Zhu
authors.forename: Bing-Ya
authors.initials: BY
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D000077209:Decitabine; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051899:Smad2 Protein / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D020413:3' Untranslated Regions; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D000077209:Decitabine; D001374:Azacitidine