title: Helicobacter pylori modulates cisplatin sensitivity in gastric cancer by down-regulating miR-141 expression.
abstract: BACKGROUND
  Recent studies found that gastric cancer patients with Helicobacter pylori infection had a better response to chemotherapy and had an improved overall prognosis compared with those without. However, the underlying mechanism remains unknown.
  
  
  METHODS
  Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression profile of miR-141 in H. pylori infected cells and tissues and their respective controls. qRT-PCR and Western blot were used to determine the expression level of KEAP-1. Luciferase reporter assays were used to determine whether KEAP-1 was a direct target of miR-141 in the gastric cancer cells. MTT and apoptosis assay were performed to detect the survival of cells under cisplatin treatment.
  
  
  RESULTS
  We found that H. pylori infection can significantly down-regulate miR-141 expression. Knockdown miR-141 expression in 7901/DDP and 7901 cells could significantly improve cisplatin sensitivity. Over-expression of miR-141 resulted in enhanced resistance to cisplatin in both gastric cancer cells. We also demonstrated that miR-141 directly targets KEAP1 by luciferase reporter assay, and that down-regulation of KEAP1 induces cisplatin resistance. Conversely, over-expression of KEAP1 significantly enhanced cisplatin sensitivity. Our 75 pairs of tissues also showed that KEAP1 was significantly up-regulated in H. pylori-positive tissues.
  
  
  CONCLUSIONS
  Altogether, these findings demonstrated that the H. pylori infection could modulate cisplatin sensitivity through miR-141-mediated regulation of KEAP1.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D016480:Helicobacter pylori / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D000072019:Kelch-Like ECH-Associated Protein 1; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
keywords: Helicobacter pylori; cisplatin sensitivity; gastric cancer; miR-141