Involvement Of APRIL In Helicobacter Pylori-related Gastric Cancer

Purpose To explore potential associations between the expression of APRIL in human Gastric cancer cell and H.pylori infection,as well as the underlying mechanism.Methods We analyzed APRIL expression levels in 200 GC tissue samples by immunohistochemistry.H.pylori infection was detected by modified Giemsa staining.The relation between APRIL and H.pylori was further assessed using the x2 test.To demonstrate whether APRIL expression is correlated with H.pylori,two gastric cancer cell lines were treated with H.pylori at three different MOIs and a C57BL/6 mice Model Colonized by H.pylori was established.The biological effects of APRIL on human GC cells in vitro and in vivo were tested by CCK-8 assay,colony formation,flow cytometry detection,transwell migration assay,matrigel invasion assay and tumour xenograft assay in animals.Western blot was used detect the mechanism of APRIL in GC.Results1.APRIL reactivity in gastric cancer tissues was obviously correlated with H.pylori infection.We also found APRIL was upregulated in human H.pylori infected GC in vitro and in vivo.2.Two human GC cell lines that one with APRIL knockdown(SGC7901-shAPRIL)and one APRIL overexpression(AGS-APRIL)was used to perform studies.In vitro and in vivo experiments showed APRIL promoted the proliferation,migration,invasion,viability,metastasis and decreased apoptosis of GC cells.3.Western blot analysis revealed that APRIL overexpression significantly upregulated the phosphorylation of AKT.Additionally,APRIL overexpression promoted the degradation of IκBα,consequently upregulated total p65 and activated NF-κB pathway,which revealed the indispensable role of APRIL in the development of GC.Conclusions Our results pointed out that the expression of APRIL,which promoted the proliferation,migration,invasion,viability and metastasis of GC cells,was upregulated in human H.pylori infected.GC through miR-145.Besides,APRIL induced gastric tumorigenicity via activating NF-κB pathway.