MicroRNA-3178 ameliorates inflammationandgastric carcinogenesis promoted by Helicobacter pylori newtoxin,Tip-, by targeting TRAF3

BackgroundHelicobacter pylori infection is the main cause of chronic gastritis, peptic ulcer, and gastric cancer. Tip- is a newly identified carcinogenic factor present in H.pylori. TRAF3 can activate NF-B by both canonical and noncanonical signaling pathways. In this study, we found that the expression of TRAF3 and NF-B was upregulated, while microRNA-3178 (miR-3178) was decreased in H.pylori-positive gastric tissues but not in H.pylori-negative tissues. Materials and MethodsGES-1 cells were incubated with 12.5g/mL recombinant Tip- (rTip-) in RPMI1640 for 2hours. After another 24hours, 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, 12.5g/mL rTip-, and collected, and the total cellular RNA and protein were extracted for the following detection. ResultsMiR-3178 mimic prevented the increasement of TRAF3 and hence decreased activation of NF-B signals, whereas miR-3178 inhibitor could not, in GES-1 cells with Tip- 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- and IL-6, which were secreted by GES-1 cells. ConclusionsTaken all together, Tip- might activate NF-B to promote inflammation and carcinogenesis by inhibiting miR-3178 expression, which directly targeting TRAF3, during H.pylori infection in gastric mucosal epithelial cells.