Abstract
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.
Data availability
The data supporting the RNA-Seq findings of this study are openly available at TCGA (https://portal.gdc.cancer.gov/). Data supporting the gene expression profile matrix files (GSE10950, GSE8671, and GSE41258) of this study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
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Acknowledgements
We are grateful to all the study participants for tissue and data donations. This work was financially supported by Chongqing Key Clinical Specialty Construction Project for Department of Oncology (No. ZDZK-202105) and a Hospital-Level Project Grant from Chongqing University Three Gorges Hospital (No. 2022YJKYXM-042).
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HZ, CB and HL designed the experiments and drafted the manuscript; CB constructed the plasmids; TZ and HZ performed western blot and qPCR experiments; CQ and XZ analyzed the data; HL, XH and QL performed animal experiments; SC and LZ performed cell culture; JG and YZ gave suggestions to the revision of the manuscript; All authors approved the final manuscript and agreed to be accountable for all aspects of the work.
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Mouse experiments were approved by the Institutional Animal Care and Use Committee of the Chongqing University Three Gorges Hospital (Chongqing, China) and were performed according to the institutional guidelines and protocols (No.SXYYDW2022-008).
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Zhang, H., Zheng, T., Qin, C. et al. CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00806-3
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DOI: https://doi.org/10.1038/s41417-024-00806-3
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