CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status

Abstract Chaperonin-containing TCP-1 (CCT) is a complex of proteins essential for cancer progression. CCT6A, the ζ subunit of CCT, contributes to tumorigenesis in various human cancers, but its function remains unclear. CCT6A had significantly higher expression in colon cancer than other CCT subunits, was upregulated in cells and clinical samples, and was correlated with an unfavorable prognosis among colon-cancer patients. GSEA results suggested that CCT6A plays a role in cellular-process signaling pathways, including the cell cycle, p53, and apoptosis. CCT6A effectively suppressed colon-cancer cell growth in vitro and in vivo; CCT6A interacted with wild-type p53 (Wtp53) and mutant p53 (Mutp53), but only inhibited Mutp53 degradation. BIRC5 was found to act downstream of CCT6A. In Wtp53 cells, CCT6A inhibition significantly reduced BIRC5 expression independent of Wtp53 levels. Conversely, in Mutp53 cells, CCT6A inhibition of BIRC5 mainly depended on Mutp53 levels; BIRC5 downregulation required Mutp53 disruption through CCT6A inhibition. Additionally, combined CCT6A knockdown and Wtp53 overexpression in Mutp53 cell lines effectively suppressed cell proliferation. It is concluded CCT6A is a potential oncogene that influences BIRC5 through distinct pathways in Wtp53 and Mutp53 cells.