title: Overexpression of human Argonaute2 inhibits cell and tumor growth.
abstract: BACKGROUND
  Argonaute (Ago) proteins are essential for the biogenesis and function of -20-30 nucleotide long RNAs such as microRNAs (miRNAs). Ago expression increases or decreases under various physiological conditions, although the functional consequences are unknown. In addition, while reduced global miRNA production was shown to enhance cellular transformation and tumorigenesis, how Ago proteins contribute to human diseases has not been reported.
  
  
  METHODS
  Ago2, an essential Ago isoform in mammals, was stably expressed in 293 T, the human embryonic kidney cell line, and H1299, the human lung adenocarcinoma cell line. miRNA and mRNA expression was investigated by quantitative PCR and microarray profiling. Cell proliferation and migration was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scratch assay in the cell cultures, respectively. How Ago2 affected cell growth in vivo was determined by H1299 xenograft tumor growth in mice. Changes in Ago2 expression in human lung cancer samples were investigated by quantitative PCR and immunohistochemistry.
  
  
  RESULTS
  Stable Ago2 overexpression elicited specific changes in miRNA and mRNA expression in both 293 T and H1299 cells. It also inhibited cell proliferation and migration in cell cultures as well as xenograft tumor growth in nude mice. Ago2 expression was lower in human lung adenocarcinomas than in the paired, non-cancerous tissues.
  
  
  CONCLUSIONS
  We concluded that changes in Ago2 expression might have significant physiological and pathological consequences in vivo.
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Paul
authors.initials: P
authors.lastname: Graves
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue