title: MicroRNA-18a modulates P53 expression by targeting IRF2 in gastric cancer patients.
abstract: OBJECTIVE
  MicroRNA-18a (miR-18a) has been reported to be upregulated in gastric cancer (GC) tissues compared with normal gastric tissues. However, little is known about its prognostic value and biological roles.
  
  
  METHODS
  In this study, miR-18a expression in gastric adenocarcinoma (GAC) tissues and adjacent non-tumor tissues was validated by in situ hybridization, and the predictive values of miR-18a were explored. The biological roles of miR-18a and the underlying signal pathway were investigated in GC cell lines.
  
  
  RESULTS
  Overexpressed intra-tumoral miR-18a was associated with poor survival rate and was an independent prognostic factor for overall survival rate (P < 0.001) in GC patients. Forced expression of miR-18a remarkably enhanced cell proliferation, migration, and invasion in GC cells, while inhibition of miR-18a caused the opposite effects. Further study showed that miR-18a suppressed the expression of interferon regulatory factor 2 (IRF2) by directly binding to its 3'-untranslated region. Moreover, miR-18a expression levels are inversely correlated with IRF2 in human GC tissues. Western blot showed that forced expression of miR-18a could not only downregulate the expression of IRF2, but also inhibit the expression of P53, suggesting that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC.
  
  
  CONCLUSIONS
  miR-18a modulated P53 expression by directly targeting IRF2 and had a high predictive value for prognosis of GAC patients. These results may lead to identification of therapeutic candidates of GC.
authors.affiliation: Department of Gastroenterology.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Li
authors.affiliation: Department of Gastroenterology.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Si-Wei
authors.initials: SW
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology.|Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Xi-Zhong
authors.initials: XZ
authors.lastname: Shen
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D000368:Aged; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D050836:Interferon Regulatory Factor-2 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D011485:Protein Binding; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; C522576:MIRN18A microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: IRF2; biomarker; gastric cancer; miR-18a; prognosis