Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation

Abstract

Background: Colorectal cancer (CRC) is the third most prevalent tumor globally. The liver is the most common site for CRC metastasis, and the involvement of the liver is a common cause of death in patients with late-stage CRC. Consequently, mitigating CRC liver metastasis (CRLM) is key to improving CRC prognosis and increasing survival. Exercise has been shown to be an effective method of improving the prognosis of many tumor types. However, the ability of exercise to inhibit CRLM is yet to be thoroughly investigated. Methods: The GSE157600 and GSE97084 datasets were used for analysis. A pan-cancer dataset which was uniformly normalized was downloaded and analyzed from the UCSC database: TCGA, TARGET, GTEx (PANCAN, n = 19,131, G = 60,499). Several advanced bioinformatics analyses were conducted, including single-cell sequencing analysis, correlation algorithm, and prognostic screen. CRC tumor microarray (TMA) as well as cell/animal experiments are used to further validate the results of the analysis. Results: The greatest variability was found in epithelial cells from the tumor group. RPS4X was generally upregulated in all types of CRC, while exercise downregulated RPS4X expression. A lowered expression of RPS4X may prolong tumor survival and reduce CRC metastasis. RPS4X and tumor stemness marker-CD44 were highly positively correlated and knockdown of RPS4X expression reduced tumor stemness both in vitro and in vivo. Conclusion: RPS4X upregulation may enhance CRC stemness and increase the odds of metastasis. Exercise may reduce CRC metastasis through the regulation of RPS4X.

Keywords

• Colorectal cancer
• Exercise
• Single-cell analysis
• Stemness
• Epithelial-mesenchymal transition
• Apoptosis