BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying...BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying mechanisms of miR-136 during this process.AIM To investigate the role of miR-136 in H.pylori-induced GC progression.METHODS GC and gastric epithelial cells were infected with H.pylori and transfected with miR-136 mimic,inhibitor,mimic plus PDCD11(identified as miR-136 target),or miR-NC(control).Cell proliferation,migration,and invasion were assessed via cell counting kit-8 assay,colony formation,wound healing,and Transwell assays.Nuclear factor kappa-B(NF-κB)/miR-136/PDCD11 interactions were confirmed by luciferase and inhibition assays.For in vivo studies H.pylori-infected BGC-823 cells were injected into nude mice.Reverse transcription PCR,western blot,immunohistochemistry,and immunofluorescent staining assay were used to assess mRNA and protein expression.RESULTS miR-136 expression was significantly upregulated while PDCD11 expression was significantly downregulated in early GC tissues and GC cells infected with H.pylori compared with non-infected tissues or cells(all P<0.01).miR-136 overexpression induced by H.pylori could promote the proliferation and migration of infected GC cells and induce the growth of H.pylori-positive GC tumors in mice while its inhibition could reverse this effect.Mechanistically,upregulation of miR-136 suppressed PDCD11 through NF-κB activation induced by H.pylori infection.CONCLUSION miR-136 is a novel diagnostic biomarker and therapeutic target in H.pylori-associated early-stage gastric carcinogenesis and acts through the NF-κB-miR-136-PDCD11 pathway.展开更多
基金Supported by the National Natural Science Foundation of China,No.82470593General Project of the Development Fund of the Affiliated Hospital of Xuzhou Medical University,No.XYFM202334.
文摘BACKGROUND MicroRNAs play an important role in gastric cancer(GC)development following Helicobacter pylori(H.pylori)infection.Yet the exact mechanism is still not fully understood.Herein,we investigated the underlying mechanisms of miR-136 during this process.AIM To investigate the role of miR-136 in H.pylori-induced GC progression.METHODS GC and gastric epithelial cells were infected with H.pylori and transfected with miR-136 mimic,inhibitor,mimic plus PDCD11(identified as miR-136 target),or miR-NC(control).Cell proliferation,migration,and invasion were assessed via cell counting kit-8 assay,colony formation,wound healing,and Transwell assays.Nuclear factor kappa-B(NF-κB)/miR-136/PDCD11 interactions were confirmed by luciferase and inhibition assays.For in vivo studies H.pylori-infected BGC-823 cells were injected into nude mice.Reverse transcription PCR,western blot,immunohistochemistry,and immunofluorescent staining assay were used to assess mRNA and protein expression.RESULTS miR-136 expression was significantly upregulated while PDCD11 expression was significantly downregulated in early GC tissues and GC cells infected with H.pylori compared with non-infected tissues or cells(all P<0.01).miR-136 overexpression induced by H.pylori could promote the proliferation and migration of infected GC cells and induce the growth of H.pylori-positive GC tumors in mice while its inhibition could reverse this effect.Mechanistically,upregulation of miR-136 suppressed PDCD11 through NF-κB activation induced by H.pylori infection.CONCLUSION miR-136 is a novel diagnostic biomarker and therapeutic target in H.pylori-associated early-stage gastric carcinogenesis and acts through the NF-κB-miR-136-PDCD11 pathway.
