Ulcerative colitis-associated
colorectal cancer (UC-CRC) is the most serious complication of
ulcerative colitis (UC). Nuclear factor of activated T cells 3 (
NFATc3) is participated in
inflammation and
cancer. In this study, we investigated the effects of
NFATc3 on experimental UC-CRC in vivo and in vitro, and explored the underlying mechanisms. Administration of
azoxymethane (AOM) and
dextran sulfate sodium (DSS) induced UC-CRC model in C57BL/6 mice.
Body weight was monitored weekly. Colon tissues were harvested at week 14. We examined changes in the histopathology, inflammatory
cytokines,
carcinogenesis factors, and epithelial-mesenchymal transition (EMT) markers in colon tissues. We found that
NFATc3 expression was significantly up-regulated in AOM/DSS treated mice compared with control. Mice lacking
NFATc3 showed decreased
tumor number and size, decreased mucosal damage, and increased survival rate. Moreover, down-regulation of
NFATc3 could inhibit the proliferation and EMT of UC-CRC, decrease the levels of pro-inflammatory
cytokines, reduce the colonic infiltration by neutrophils and macrophages, and suppress the activation of P38 and JNK signal pathway in mice. In In vitro experiments, silencing
NFATc3 suppressed the proliferation and EMT of CRC cells, and reduced the activation of P38 and JNK. In addition, miR-370-3p could bind to
NFATc3. Down-regulation of miR-370-3p promoted proliferation and EMT of CRC cells, while silencing
NFATc3 could reverse these effects. In conclusion,
NFATc3 was involved in the pathogenesis of experimental UC-CRC and
NFATc3 knockdown ameliorated experimental UC-CRC progression via the inhibition of inflammatory responses and EMT.
NFATc3 mediated the inhibitory effects of miR-370-3p on CRC cells proliferation and EMT. Targeting
NFATc3 may be effective in treating UC-CRC.