Introduction:Ulcerative colitis (UC) is a chronic and inflammatory bowel disease. UC-associated colorectal cancer (UC-CRC) is one of the most severe complications of long-standing UC. In the present study, we explored the effects of miR-33p on UC-CRC in vivo and investigated its underlying mechanisms in vivo and in vitro.
Methods:Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to induce UC-CRC in C57BL/6 mice. AOM/DSS-induced mice were treated with 5×108 pfu miR-33p overexpressing-adenovirus via tail-vein injection every two weeks.
Results:We found that miR-33p significantly improved the body weights and survival rates and inhibited the tumorigenesis of UC-CRC in AOM/DSS mice. Mechanically, miR-33p inhibited AOM/DSS-induced inflammatory response by decreasing tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) through targeting toll-like receptor 4 (TLR4), as demonstrated by down-regulation of TLR4, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and phosphorylated epidermal growth factor receptor (pEGFR). miR-33p decreased the expression of tumor-associated proteins, including p53, β-catenin, and ki67 in AOM/DSS-treated mice. Additionally, miR-33p remarkably inhibited epithelial-mesenchymal transition (EMT) via increasing E-cadherin expression and reducing N-cadherin and Vimentin expression in vivo. Further studies showed that miR-33p repressed proliferation and EMT of colon cancer cells in vitro. Moreover, we proved that miR-33p decreased the expression of tumor-associated proteins and reversed EMT by regulating β-catenin in colon cancer cells.
Conclusion:Taken together, miR-33p alleviated UC-CRC by inhibiting the inflammatory response and EMT in mice, which suggested miR-33p as a novel potential target for UC-CRC therapy.
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