Downregulation of MUC1 Enhances Antitumor Response in Colon Cancer Model by Decreasing PD-L1 Expression In Vivo and In Vitro.

Colorectal cancer (CRC) is a cancer with poor 5-year survival rates. The exploration of biomarkers and potential mechanisms for the diagnosis and treatment of CRC is crucial in clinical practice. The transmembrane glycoprotein Mucin 1 (MUC1), as a glycoprotein, is essential for controlling tumor metabolism. Multiple studies demonstrate that MUC1 has an antitumor effect in prostate, breast, and gastric cancers. However, the mechanism of MUC1 in CRC is still unclear. This study was to explore MUC1's putative molecular mechanism in CRC. The expression of MUC1 in the tumor specimens or normal tissues was identified by immunohistochemistry and Western blot. MUC1 knockdown or exogenous expression and miR-200c were performed to confirm MUC1 function. The molecular mechanism of MUC1 was revealed through quantitative real-time PCR (Q-PCR), western blot, immunoprecipitation assays, and flow cytometry. Our results showed positive correlation between the expression of PD-L1 and MUC1, which is increased in colon carcinoma tissues. MUC1 upregulation can promote CD8 + T cell immune tolerance and immune failure, as well as increased infiltration of Treg, MDSCs and ATM cells. Furthermore, MUC1 downregulated PD-L1 expression by NF-κB p65 and miR-200c. MUC1 downregulation improved antitumor immune response of CD8 + T cells and decreased the proportion of Treg, MDSCs, and ATM cell infiltration. Downregulating MUC1 enhances antitumor immune response through NF-κB p65, and mirR-200c by reducing PD-L1 expression.