CCT8 drives colorectal cancer progression via the RPL4-MDM2-p53 axis and immune modulation

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genomics

Background:

• Colorectal cancer (CRC) presents a significant global health challenge, necessitating novel therapeutic targets.
• Understanding the molecular mechanisms driving CRC progression is crucial for developing effective interventions.

Purpose of the Study:

• To investigate the oncogenic role of CCT8 in colorectal cancer (CRC).
• To elucidate the interaction between CCT8 and RPL4 within the RPL4-MDM2-p53 signaling pathway in CRC.

Main Methods:

• Utilized TIMER 2.0, TCGA, and GTEx databases for CCT8 expression analysis in CRC.
• Performed immunohistochemistry, cell proliferation, migration, invasion, and apoptosis assays.
• Employed gene set enrichment, protein-protein interaction, co-immunoprecipitation, and gene set variation analyses to explore molecular mechanisms and immune infiltration.

Main Results:

• CCT8 expression is significantly elevated in CRC tissues and correlates with tumor progression.
• CCT8 and RPL4 exhibit a positive correlation and similar immune infiltration patterns, suggesting synergistic action.
• CCT8 and RPL4 influence the RPL4-MDM2-p53 axis, promoting p53 ubiquitination and degradation.

Conclusions:

• CCT8 plays a significant oncogenic role in colorectal cancer.
• The findings highlight CCT8's molecular mechanisms involving the RPL4-MDM2-p53 pathway, offering potential therapeutic avenues for CRC.