title: MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer.
abstract: BACKGROUND
  A thorough understanding of gastric cancer at the molecular level is urgently needed. One prominent oncogenic microRNA, miR-21, was previously reported to be upregulated in gastric cancer.
  
  
  METHODS
  We performed an unbiased search for downstream messenger RNA targets of miR-21, based on miR-21 dysregulation, by using human tissue specimens and the MKN28 human gastric carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN28 with miR-21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by flow cytometry and luciferase reporter assay.
  
  
  RESULTS
  This search identified Serpini1 as a putative miR-21 target. Luciferase assays demonstrated direct interaction between miR-21 and Serpini1 3'UTR. miR-21 and Serpini1 expression levels were inversely correlated in a subgroup of gastric cancers, suggesting a regulatory mechanism that included both of these molecules. Furthermore, Serpini1 induced growth retardation of MKN28 and induced vigorous G1/S arrest suggesting its potential tumour-suppressive function in the stomach.
  
  
  CONCLUSIONS
  Taken together, these data suggest that in a subgroup of gastric cancers, miR-21 is upregulated, inducing downregulation of Serpini1, which in turn releases the G1-S transition checkpoint, with the end result being increased tumour growth.
authors.affiliation: Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Sumitaka
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Alexandru V
authors.initials: AV
authors.lastname: Olaru
authors.forename: Fangmei
authors.initials: F
authors.lastname: An
authors.forename: Delgermaa
authors.initials: D
authors.lastname: Luvsanjav
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Rachana
authors.initials: R
authors.lastname: Agarwal
authors.forename: Ciprian
authors.initials: C
authors.lastname: Tomuleasa
authors.forename: Irinel
authors.initials: I
authors.lastname: Popescu
authors.forename: Sorin
authors.initials: S
authors.lastname: Alexandrescu
authors.forename: Simona
authors.initials: S
authors.lastname: Dima
authors.forename: Mihaela
authors.initials: M
authors.lastname: Chivu-Economescu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Montgomery
authors.forename: Michael
authors.initials: M
authors.lastname: Torbenson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
authors.forename: Florin M
authors.initials: FM
authors.lastname: Selaru
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D000097522:Neuroserpin
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D009479:Neuropeptides; D012333:RNA, Messenger; D015843:Serpins; D000097522:Neuroserpin; C524940:MIRN21 microRNA, human