The Role Of MiRNA-149-3p In Gastritis And Gastric Cancer

Gastric inflammatory is a very common disease in digestive system.Many studies have shown that chronic gastric inflammatory increase the risk of gastric cancer(GC).Thus,it is meaningful to study the occurrence and development of the gastric inflammatory.NF-?B signaling pathway is well-known for its close relationship with inflammation and cancer.There many kinds of gene transcribed by NF-?B pathway are participate in the regulation of the physiological process of gastric inflammatory and GC.MicroRNA,which as a kind of non-coding RNA.Although miRNA do not encode protein,it can target the 3'-UTR or 5'-UTR of the target gene through base-paring,which can participate in the regulation of the physiological process.Besides,many studies have shown that miRNAs are widely involved in the process of inflammation and cancer.Here,We declare that miRNA-149-3p can inhibit the gastric inflammatory through antagonizing NF-?B signaling pathway.Our work are including the experiments in vivo and in vitro.In vivo,the WT mice and 149-3P KO mice are treated by LPS.The result show that mice which lacking of miR-149-3p were much more sensitive to LPS-induced acute gastric inflammatory than WT mice.These Pro-inflammatory genes,such as COX-2,iNOS,MCP-1 which are the downstream genes of NF-?B pathway,were much more improved in KO mice than the WT mice.Besides,this trend was also confirmed after pathological analysis of the respective tissues of WT mice and KO.To further investigate the function of miR-149-3p in vivo,we used miR-149-3p agomir to increase the expression level of miR-149-3p.After treated by LPS,the result show that miR-149-3p can inhibit the expression of Pro-inflammatory genes induced by LPS.In vitro,we use the agomir of miR-149-3p to investigate the function of miR-149-3p.After overexpressed miR-149-3p in GC cell SGC7901,some genes,such as MMP1?MCP-1?IFN-?,have been inhibited even after treated by LPS.Besides,we use TNFa to activate the NF-?B pathway in SGC7901,these genes which are the downstream genes of NF-?B pathway have been significantly inhibited with overexpressed miR-149-3p.After that,overexpressed miR-149-3p can inhibited the phosphorylation of I?B? In the luciferase assay,overexpressed miR-149-3p can antagonize the transactivity of NF-?B pathway.In conclusion,our work has shown that miRNA-149-3p can be a repressor of NF-?B pathway in gastric inflammatory.These findings give us way to treat gastric inflammatory.