Abstract

The ubiquitin (Ub)–proteasome system (UPS) is an important regulatory component in colorectal cancer (CRC), and the cell cycle is also characterized to play a significant role in CRC. In this present study, we firstly identified UPS-associated differentially expressed genes and all the differentially expressed protein-coding genes in CRC through three differential analyses. UPS-associated genes were also further analyzed via survival analysis. A weighted gene co-expression network analysis (WGCNA) was used to identify the cell cycle-associated genes. We used protein–protein interaction (PPI) network to comprehensively mine the potential mechanism of the UPS–cell cycle regulatory axis. Moreover, we constructed a signature based on UPS-associated genes to predict the overall survival of CRC patients. Our research provides a novel insight view of the UPS and cell cycle system in CRC.

Highlights

  • The ubiquitin (Ub)–proteasome system (UPS) is identified to regulate the cellular protein by ubiquitination modification

  • Through the weighted gene co-expression network analysis (WGCNA) process, we identified six modules, and the cell cycle-related biological pathways obtained from the gene set enrichment analysis (GSEA) based on the all dysregulated protein-coding genes were set as reference

  • Colorectal cancer is identified as one digestive system cancer type that has high morbidity and mortality (Siegel et al, 2020)

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Summary

Introduction

The ubiquitin (Ub)–proteasome system (UPS) is identified to regulate the cellular protein by ubiquitination modification. Ub is an important component in the UPS. It consists of a 76-aminoacid protein and is usually highly conserved in eukaryotes (Zheng and Shabek, 2017). Among the UPS, three significant enzymes function as enzyme cascade to transmit the Ub to the substrate. The UPS process can be summarized as follows: at first, E1 activates Ub and transmits it to E2 by an adenosine triphosphate-dependent way. E3 are usually identified as the most crucial component among the three-enzyme cascade because the interaction between E3 and the substrate is highly specific, and the ubiquitination of the substrate mainly depends on the E3

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