The Potential Biological Roles and Clinical Significance of Anaphase-Promoting Complex Subunit 1 in Colorectal Cancer.

BackgroundAnaphase-promoting complex subunit 1 (ANAPC1) is a regulator of cellular mitosis and an important factor in tumorigenesis. To date, a comprehensive assessment of the potential role, biological behaviours, and clinical significance of ANAPC1 in colorectal cancer (CRC) is still lacking.Materials and methodsThis study integrated 2329 mRNA expression data, single-cell RNA sequencing (scRNA-seq), and internal immunohistochemistry of 416 tissue samples to comprehensively evaluate the abnormal expression pattern of ANAPC1 in CRC. It also incorporated evidence from immune infiltration analysis, functional enrichment analysis, and weighted gene co-expression network analysis to explore the biological behaviour of ANAPC1 in CRC. In addition, in vitro cell biology experiments such as real-time polymerase chain reaction (RT-PCR), western blot (WB), cholecystokinin 8 (CCK-8), wound healing, cell cycle, and apoptosis assays were conducted to verify the potential effect of ANAPC1 on CRC cells.ResultsANAPC1 mRNA was significantly overexpressed in CRC tissue (SMD = 2.07, 95% CI 1.59-2.55, < .05) and malignant epithelial cells ( < .05). Validation at the protein level similarly confirmed the overexpression of ANAPC1 in CRC tissue ( < .05). ANAPC1 in CRC may play a role in abnormal ribosome biogenesis, DNA replication, ATP-dependent activity acting on DNA, nuclear division, chromosome segregation, and other pathways. In vitro experiments demonstrated that HCT-116 cells with ANAPC1 knockdown had reduced proliferation and migration abilities, increased cell apoptosis rate, and altered cell cycle distribution. In addition, CRC patients with low ANAPC1 expression were more likely to benefit from treatment with immune checkpoint inhibitors. ANAPC1 was significantly downregulated in malignant epithelial cells of CRC treated with PD-1 inhibitors ( < .05).ConclusionANAPC1 may have a positive impact on the development of CRC by being involved in pathways related to DNA replication, chromosome segregation, and ribosomes.