含有伴侣蛋白的 TCP1 (CCT) 是一种多亚基复合物，已知参与许多蛋白质的正确折叠。目前，CCT 亚基在癌症进展中的机制尚不完全清楚。根据数据分析，发现CCT亚基6 A（CCT6A）的表达高于CCT的其他亚基，并且与结肠癌的不良预后相关。在这里，我们发现 CCT6A 沉默可在体外和体内抑制结肠癌增殖和存活表型。 CCT6A 在细胞过程中发挥作用，包括细胞周期、p53 和凋亡信号通路。进一步的研究表明 CCT6A 与 Wtp53 和 Mutp53 直接结合，并且发现 BIRC5 在 CCT6A 下游发挥作用。亮点是 CCT6A 抑制显着降低了 Wtp53 细胞中 BIRC5 的表达，与 Wtp53 水平无关。相反，在Mutp53细胞中，CCT6A抑制对BIRC5的下调主要取决于Mutp53水平。此外，Mutp53 细胞系中 CCT6A 抑制和 Wtp53 过表达相结合可有效抑制细胞增殖。结论是 CCT6A 是一种潜在的癌基因，通过 Wtp53 和 Mutp53 细胞中的不同途径影响 BIRC5。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

Chaperonin-containing TCP1 (CCT) is a multi-subunit complex, known to participate the correct folding of many proteins. Currently, the mechanism underlying CCT subunits in cancer progression is incompletely understood. Based on data analysis, the expression of CCT subunit 6 A (CCT6A) is found higher than the other subunits of CCT and correlated with an unfavorable prognosis in colon cancer. Here, we find CCT6A silencing suppresses colon cancer proliferation and survival phenotype in vitro and in vivo. CCT6A plays a role in cellular process, including the cell cycle, p53, and apoptosis signaling pathways. Further investigations have shown direct binding between CCT6A and both Wtp53 and Mutp53, and BIRC5 is found to act downstream of CCT6A. The highlight is that CCT6A inhibition significantly reduces BIRC5 expression independent of Wtp53 levels in Wtp53 cells. Conversely, in Mutp53 cells, downregulation of BIRC5 by CCT6A inhibition mainly depends on Mutp53 levels. Additionally, combined CCT6A inhibition and Wtp53 overexpression in Mutp53 cell lines effectively suppresses cell proliferation. It is concluded CCT6A is a potential oncogene that influences BIRC5 through distinct pathways in Wtp53 and Mutp53 cells.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.