title: miR-494 acts as an anti-oncogene in gastric carcinoma by targeting c-myc.
abstract: BACKGROUND
  We recently showed that miR-494 was downregulated in gastric carcinoma (GC). The objectives of this study were to determine the role of miR-494 in GC malignancy and to identify its target genes.
  
  
  METHODS
  Real-time polymerase chain reaction was employed to quantify the expression level of miR-494 and c-myc in gastric cancer tissues. Bioinformatics was used to predict the downstream target genes of miR-494, which were confirmed by luciferase and RNA immunoprecipitation assays. Cell functional analyses and a xenograft mouse model were used to evaluate the role of miR-494 in malignancy.
  
  
  RESULTS
  miR-494 was downregulated in human GC tissues and in GC cells and was negatively correlated with c-myc expression. High level of c-myc or low level of miR-494 correlated with poor prognosis. The miR-494-binding site in the c-myc 3' untranslated region was predicted using TargetScan and was confirmed by the luciferase assay. Additionally, c-myc and miR-494 were enriched in coimmunoprecipitates with tagged Argonaute2 proteins in cells overexpressing miR-494. Furthermore, a miR-494 mimic significantly downregulated endogenous c-myc expression, which may contribute to the delayed G1/S transition, decreased synthesis phase bromodeoxyuridine incorporation, and impaired cell growth and colony formation; on the other hand, treatment with a miR-494 inhibitor displayed the opposite effects. Reduced tumor burden and decreased cell proliferation were observed following the delivery of miR-494 into xenograft mice.
  
  
  CONCLUSIONS
  miR-494 is downregulated in human GC and acts as an anti-oncogene by targeting c-myc. miR-494 plays a role in the pathogenesis of gastric cancer in a recessive fashion.
authors.affiliation: Department of Gastrointestinal and Pancreatic Surgery, Centre of Gastric Cancer, The First Affiliated Hospital, Guangzhou, Guangdong, China.
authors.forename: Weiling
authors.initials: W
authors.lastname: He
authors.forename: Yuhuang
authors.initials: Y
authors.lastname: Li
authors.forename: Xinlin
authors.initials: X
authors.lastname: Chen
authors.forename: Liya
authors.initials: L
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Wang
authors.forename: Yunbao
authors.initials: Y
authors.lastname: Pan
authors.forename: Shirong
authors.initials: S
authors.lastname: Cai
authors.forename: Yulong
authors.initials: Y
authors.lastname: He
authors.forename: Zunfu
authors.initials: Z
authors.lastname: Ke
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009368:Neoplasm Transplantation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*
chemical_list: D020413:3' Untranslated Regions; C547168:MIRN494 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc
keywords: c-myc; gastric cancer; miR-494; microRNAs