title: MicroRNA-3178 ameliorates inflammation and gastric carcinogenesis promoted by Helicobacter pylori new toxin, Tip-α, by targeting TRAF3.
abstract: BACKGROUND
  Helicobacter pylori infection is the main cause of chronic gastritis, peptic ulcer, and gastric cancer. Tip-α is a newly identified carcinogenic factor present in H. pylori. TRAF3 can activate NF-κB by both canonical and noncanonical signaling pathways. In this study, we found that the expression of TRAF3 and NF-κB was upregulated, while microRNA-3178 (miR-3178) was decreased in H. pylori-positive gastric tissues but not in H. pylori-negative tissues.
  
  
  METHODS
  GES-1 cells were incubated with 12.5 μg/mL recombinant Tip-α (rTip-α) in RPMI1640 for 2 hours. After another 24 hours, the supernatant medium was designed as inflammatory-conditioned medium (ICM) and that from the untreated control cells was designed as untreated control medium. The release of proinflammatory cytokines from GES-1 cells and proliferation of gastric cancer cells was determined by ELISA and CCK-8 kits. Cells were transfected with the mimic, inhibitor, negative control of miR-3178, or TRAF3 siRNA control siRNA. The medium was then replaced with RPMI1640, 12.5 μg/mL rTip-α, and collected, and the total cellular RNA and protein were extracted for the following detection.
  
  
  RESULTS
  MiR-3178 mimic prevented the increasement of TRAF3 and hence decreased activation of NF-κB signals, whereas miR-3178 inhibitor could not, in GES-1 cells with Tip-α treatment. The condition medium from miR-3178 mimic transfected GES-1 cells could inhibit proliferation and induce apoptosis of inflammation-related gastric cancer cells SGC7901 and MGC803 by decreasing the production of inflammatory cytokines TNF-α and IL-6, which were secreted by GES-1 cells.
  
  
  CONCLUSIONS
  Taken all together, Tip-α might activate NF-κB to promote inflammation and carcinogenesis by inhibiting miR-3178 expression, which directly targeting TRAF3, during H. pylori infection in gastric mucosal epithelial cells.
authors: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
authors: Meijuan
authors: M
authors: Zou
authors: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Fang
authors: F
authors: Wang
authors: Medical School of Nanjing University, Nanjing, China.
authors: Aiqin
authors: A
authors: Jiang
authors: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
authors: Anliang
authors: A
authors: Xia
authors: Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
authors: Siya
authors: S
authors: Kong
authors: Nanjing University of Chinese Medicine, Nanjing, China.
authors: Chun
authors: C
authors: Gong
authors: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Mingxia
authors: M
authors: Zhu
authors: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Xin
authors: X
authors: Zhou
authors: Department of Radiation Oncology, Jiangsu Cancer Hospital, Nanjing, China.
authors: Jun
authors: J
authors: Zhu
authors: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Wei
authors: W
authors: Zhu
authors: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Wenfang
authors: W
authors: Cheng
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; C000602532:MIRN3178 microRNA, human; D035683:MicroRNAs; D048008:TNF Receptor-Associated Factor 3; C090656:TRAF3 protein, human
keywords: 
  Helicobacter pylori
  ; microRNA-3178; nuclear factor kappa-light-chain-enhancer of activated B cells; tumor necrosis factor receptor-associated factor 3; tumor necrosis factor-α-inducing protein