title: MiR-223 promotes the cisplatin resistance of human gastric cancer cells via regulating cell cycle by targeting FBXW7.
abstract: BACKGROUND
  Increasing evidence showed that miRNAs serve as modulators of human cancer, either as oncogene or tumor suppressors. Cisplatin resistance is the most common cause of chemotherapy failure in gastric cancer (GC). However, the roles of miRNAs in cisplatin resistance of GC remain largely unknown. The aim of the study was to identify a novel miRNA/gene pathway that regulates the sensitivity of GC cells to cisplatin.
  
  
  METHODS
  In this study, we chose miR-223 by qRT-PCR analysis, the most significantly up-regulated miRNA in GC, to investigate its formation of DDP-resistant phenotype of GC cells and possible molecular mechanisms.
  
  
  RESULTS
  We found that miR-223 was most significantly up-regulated miRNA in DDP-resistant GC cells compared with parental GC cells. Besides, its expression was also significantly up-regulated in GC tissues. FBXW7 was identified as the direct and functional target gene of miR-223. Overexpression of FBXW7 could mimic the effect of miR-223 down-regulation and silencing of FBXW7 could partially reverse the effect of miR-223 down-regulation on DDP resistance of DDP-resistant GC cells. Besides, miR-223 and FBXW7 could affect the G1/S transition of cell cycle by altering some certain cell cycle regulators. Furthermore, miR-223 was found to be significantly up-regulated in H. pylori infected tissues and cells, suggesting that H. pylori infection may lead to GC development and DDP resistance.
  
  
  CONCLUSIONS
  Our findings revealed the roles of miR-223/FBXW7 signaling in the DDP resistance of GC cells and targeting it will be a potential strategic approach for reversing the DDP resistance in human GC.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. zhouxiaoying0926@sina.cn.|First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China. zhouxiaoying0926@sina.cn.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. jinwujuanzxy@163.com.|First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China. jinwujuanzxy@163.com.
authors.forename: Wujuan
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Digestive Endoscopy Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. jiahongyanzxy@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. yanjinzxy@163.com.|First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China. yanjinzxy@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. guoxinz@njmu.edu.cn.|First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China. guoxinz@njmu.edu.cn.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D044783:F-Box Proteins / Q000737:chemistry / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009367:Neoplasm Staging; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D002945:Cisplatin; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D035683:MicroRNAs; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; C513273:FBXW7 protein, human; C525067:MIR223, human