IL-22 induces colon cancer proliferation through STAT3 and PRC2 signaling (TUM10P.1036)

Abstract

Abstract Background: IL-22(interleukin-22) is a newly identified cytokine which has been recently highlighted owing to its biological significance in carcinogenesis. However, the role of IL-22 in colon cancer proliferation has remained unclear. Since both JAK-STAT signaling and Polycomb Repression complex (PRC) 2 play crucial roles in epithelial proliferation. We investigated the mechanism by which IL-22 induces colon cancer proliferation. Methods: Colon cancer cells proliferation was detected by FACS and H3 Thymidine Incorporation. Cell cycle related genes were tested by Real-Time PCR. Lentiviral vector encoding gene specific shRNAs (STAT3, EZH2, SUZ12) and scramble particles were used to transfect colon cancer cells. ChIP assays were performed to detect the binding of different proteins and DNA. Results: IL-22 significantly induces colon cancer cells proliferation through STAT3 signaling. This increased proliferation involved the inhibition of p16 and p18 through aberrant promoter histone methylation H3K27me3. PRC2 catalyzes promoter H3K27me3 of p16 and p18, which can be up-regulated by IL-22. Furthermore, STAT3 can bind to PRC2 members (SUZ12 and EED), which also can be up-regulated by IL-22 stimulation. Conclusion: IL-22 can induce human colon cancer cells proliferation by activation of STAT3, which was phosphorylated and directed bind to the PRC2 complex, especially SUZ12 and EED, and consequently catalyzed the H3K27m3 of cell cycle check-point genes p16 and p18.