RT Journal Article SR Electronic T1 Circ-KRT6C promotes malignant progression and immune evasion of colorectal cancer through miR-485-3p/PDL1 axis JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP JPET-AR-2021-000518 DO 10.1124/jpet.121.000518 A1 Zhipeng Jiang A1 Zehui Hou A1 Wei Liu A1 Zhuomin Yu A1 Zhiqiang Liang A1 Shuang Chen YR 2021 UL http://jpet.aspetjournals.org/content/early/2021/03/26/jpet.121.000518.abstract AB Background: circular RNA was reported to be a significant participant in the development of tumorigenesis, including colorectal cancer. Therefore, we aimed to clarify the precise role and effects of circ-keratin 6C in colorectal cancer progression. Methods: The relative expression levels of circ-KRT6C, microRNA-16-5p, and programmed cell death receptor ligand 1 were analyzed by real-time quantitative polymerase chain reaction along withand western blot assays. The proliferation was assessed by cell count kit 8 and colony-forming assays. The apoptotic cells were determined by flow cytometry assay. The migration and invasion were analyzed by transwell assay. Colorectal cancer cells were co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells to assess immune response. The interaction relationships among circ-KRT6C, miR-485-3p, and PDL1 were examined by dual-luciferase reporter assay. effects of circ-KRT6C inhibition in vivo was analyzed by an in vivo animal experiment. Results: Circ-KRT6C was overexpressed in colorectal cancer tissues and cells, and its level was associated with overall survival time of colorectal cancer patients. The suppression of circ-KRT6C suppressed growth, migration, invasion, and immune escape while stimulated apoptosis in colorectal cancer cells, which was abolished by shortage of miR-485-3p. In addition, overexpression of miR-485-3p repressed malignant progression and immune evasion of colorectal cancer by targeting PDL1, implying that PDL1 was a functional target of miR-485-3p. A xenograft experiment also suggested that circ-KRT6C inhibition could repress tumor growth in vivo. Conclusion: Circ-KRT6C could increase PDL1 expression by functioning as a miR-485-3p sponge, which promoted malignant progression and immune evasion of colorectal cancer cells. Significance Statement Circ-KRT6C could increase PDL1 expression by functioning as a miR-485-3p sponge, which promoted malignant progression and immune evasion of colorectal cancer.