Complement factor I knockdown inhibits colon cancer development by affecting Wnt/β-catenin/c-Myc signaling pathway...

Colon cancer (CC) occurrence and progression are considerably influenced by the tumor microenvironment. However, the exact underlying regulatory mechanisms remain unclear.

To investigate immune infiltration-related differentially expressed genes (DEGs) in CC and specifically explored the role and potential molecular mechanisms of complement factor I (CFI).

Immune infiltration-associated DEGs were screened for CC using bioinformatics. Quantitative reverse transcription polymerase chain reaction was used to examine hub DEGs expression in the CC cell lines. Stable CFI-knockdown HT29 and HCT116 cell lines were constructed, and the diverse roles of CFI in vitro were assessed using CCK-8, 5-ethynyl-2'-deoxyuridine, wound healing, and transwell assays. Hematoxylin and eosin staining and immunohistochemistry staining were employed to evaluate the influence of CFI on the tumorigenesis of CC xenograft models constructed using BALB/c male nude mice. Key proteins associated with glycolysis and the Wnt pathway were measured using western blotting.

Six key immune infiltration-related DEGs were screened, among which the expression of CFI, complement factor B, lymphoid enhancer binding factor 1, and SRY-related high-mobility-group box 4 was upregulated, whereas that of fatty acid-binding protein 1, and bone morphogenic protein-2 was downregulated. Furthermore, CFI could be used as a diagnostic biomarker for CC. Functionally, CFI silencing inhibited CC cell proliferation, migration, invasion, and tumor growth. Mechanistically, CFI knockdown downregulated the expression of key glycolysis-related proteins (glucose transporter type 1, hexokinase 2, lactate dehydrogenase A, and pyruvate kinase M2) and the Wnt pathway-related proteins (β-catenin and c-Myc). Further investigation indicated that CFI knockdown inhibited glycolysis in CC by blocking the Wnt/β-catenin/c-Myc pathway.

The findings of the present study demonstrate that CFI plays a crucial role in CC development by influencing glycolysis and the Wnt/β-catenin/c-Myc pathway, indicating that it could serve as a promising target for therapeutic intervention in CC.