Role of microRNAs in Resveratrol-Mediated Mitigation of Colitis-Associated Tumorigenesis in ApcMin/+ Mice

摘要: The pleiotropic effects of resveratrol include anti-inflammatory, antioxidant, and anticancer activities, thus unique possibilities exist to explore mechanistic pathways chemoprevention. aim this study was investigate the role microRNA (miRNA) alterations induced by in context chemopreventive mechanisms against dextran sodium sulfate (DSS)-induced colitis-associated tumorigenesis Apc(Min/+) mouse. To that end, mice were exposed 2% DSS enhance intestinal inflammation polyp development. Concurrently, received either vehicle or treatment via oral gavage for 5 weeks. Interestingly, DSS-exposed with resulted decreased number size polyps, fewer histologic signs cell damage, proliferating epithelial cells mucosa compared vehicle. Resveratrol dramatically reversed on numbers specific inflammatory CD4(+) T cells, CD8(+) B natural killer myeloid-derived suppressor mesenteric lymph nodes. also interleukin-6 (IL-6) tumor necrosis factor-α protein levels reduced IL-6 cyclooxygenase-2 mRNA expression. Microarray analysis revealed 104 miRNAs exhibiting >1.5-fold differences expression tissue resveratrol-treated mice. Among them, two anti-inflammatory properties, miRNA-101b miRNA-455, validated be upregulated reverse-transcription polymerase chain reaction. Pathway numerous differentially regulated targeted mRNAs associated processes known roles tumorigenesis. These results suggest mediates properties suppresses through miRNA modulation.