Circ_0005576 Promotes Malignant Progression Through miR-874/CDK8 Axis in Colorectal Cancer

PURPOSE: To investigate the function of circ_0005576 in colorectal cancer (CRC) progression. PATIENTS AND METHODS: Circ_0005576 expression in CRC patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). CRC cells were transfected using Lipofectamine 2000 reagent. CRC cell proliferation was researched by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2-deoxy-uridine (EdU) incorporation experiment. Cell cycle and apoptosis were determined by flow cytometry analysis. Luciferase reporter assay was used to explore the relationship between circ_0005576 and miR-874 or between miR-874 and CDK8. qRT-PCR and Western blot were used to detect circ_0005576, miR-874, and CDK8 expression. In vivo experiments were performed using nude mice. CDK8 and Ki67 expression in xenograft tumors was investigated by immunohistochemistry. Tunel assay was conducted to analyze the apoptosis of xenograft tumors. RESULTS: Circ_0005576 expression was up-regulated in CRC, which was associated with tumor progression (P < 0.05 or P < 0.01). Circ_0005576 knockdown in CRC cells reduced proliferation, induced apoptosis, increased cells in the G1 phase, and decreased cells in the S phase (P < 0.01 or P < 0.001). Circ_0005576 promoted CDK8 expression via sponging miR-874. miR-874 knockdown and CDK8 overexpression significantly reversed the inhibitory effect of circ_0005576 knockdown on CRC cells malignant phenotype (P < 0.05 or P < 0.01). Circ_0005576 knockdown inhibited tumor growth in vivo (P < 0.01). Circ_0005576 knockdown reduced CDK8, Ki67 expression, and enhanced apoptosis in xenograft tumors. CONCLUSION: Circ_0005576 promoted malignant progression through the miR-874/CDK8 axis in CRC.