The Exploration Of The Effect Of IL-33 On The Regulation Of Cell Proliferation In Colorectal Cancer

Interleukin-33?IL-33?was involved in various types of diseases including cancer.A series studies of IL-33 in cancers have mainly focused on its immune regulation in which IL-33promoted cancer development.The signals that IL-33 triggerd in cancer cells were still poorly unknown.By analyzing TCGA data,we carried on gene enrichment analysis?GSEA?and found that IL-33 expression in human colorectal cancer?CRC?tissues was positively correlated with the genes involved in cell proliferation.The MC38 xenograft tumors in IL-33 transgenic mice grew significantly rapidly than that in wild-type mice.In vitro experiments demonstrated that IL-33 could directly accelerate the proliferation of primary CRC cells and CRC cell lines.IL-33 promoted cycloxygenase-2?COX2?expression and consequently enhanced prostaglandin E2?PGE₂?production.Blocking assays showed that the proliferation acceleration caused by IL-33 was COX2/PGE₂-dependent.Mechanistically,IL-33 acts via its functional receptor ST2 expressing on CRC cells to increase the expression of COX2 by stimulating NF-?B signaling pathway.Together,we report a direct proliferation-promoting role of IL-33 in CRC.