A Comprehensive Pan-Cancer Analysis of the Regulation and Prognostic Effect of Coat Complex Subunit Zeta 1

Abstract

The Coatomer protein complex Zeta 1 (COPZ1) has been reported to play an essential role in maintaining the survival of some types of tumors. In this study, we sought to explore the molecular characteristics of COPZ1 and its clinical prognostic value through a pan-cancers bioinformatic analysis. We found that COPZ1 was extremely prevalent in a variety of cancer types, and high expression of COPZ1 was linked to poor overall survival in many cancers, while low expression in LAML and PADC was correlated with tumorigenesis. Besides, the CRISPR Achilles’ knockout analysis revealed that COPZ1 was vital for many tumor cells’ survival. We further demonstrated that the high expression level of COPZ1 in tumors was regulated in multi-aspects, including abnormal CNV, DNA-methylation, transcription factor and microRNAs. As for the functional exploration of COPZ1, we found a positive relationship between COPZ1’s expression and stemness and hypoxia signature, especially the contribution of COPZ1 on EMT ability in SARC. GSEA analysis revealed that COPZ1 was associated with many immune response pathways. Further investigation demonstrated that COPZ expression was negatively correlated with immune score and stromal score, and low expression of COPZ1 has been associated to more antitumor immune cell infiltration and pro-inflammatory cytokines. The further analysis of COPZ1 expression and anti-inflammatory M2 cells showed a consistent result. Finally, we verified the expression of COPZ1 in HCC cells, and proved its ability of sustaining tumor growth and invasion with biological experiments. Our study provides a multi-dimensional pan-cancer analysis of COPZ and demonstrates that COPZ1 can serve as both a prospective target for the treatment of cancer and a prognostic marker for a variety of cancer types.

Mechanism and endoscopic‐treatment‐induced evolution of biliary non‐anastomotic stricture after liver transplantation revealed by single‐cell RNA sequencing

“…The significant reduction in the proportion of EC exacerbates the ischemic and hypoxic conditions of the tissue. Almost all cell types exhibited upregulation of the COPZ1 gene, which is associated with hypoxia 24 . We also discovered that the wound healing ability, response to transforming growth factor‐beta and negative regulation of phosphate metabolism functions of the epithelial cells in the STT group were inhibited.…”

“…Almost all cell types exhibited upregulation of the COPZ1 gene, which is associated with hypoxia. 24 We also discovered that the wound healing ability, response to transforming growth factor‐beta and negative regulation of phosphate metabolism functions of the epithelial cells in the STT group were inhibited. Importantly, we found that after ET, the response of these cells to oxygen levels was downregulated, which played a crucial role in the recovery of the functions of parenchymal and mesenchymal cells.…”

Chemoproteomics enables identification of coatomer subunit zeta‐1 targeted by a small molecule for enterovirus A71 inhibition

“… 22 , 40 Although COPZ1 resides in the cytosol in both free and coatomer‐bound forms, unlike the other six coatomer subunits, COPZ1 functions as an integral complex of the coatomer for COPI‐coated vesicle assembly and protein trafficking within the secretory pathway. To date, some investigations of COPZ1 have indicated that COPZ1 is a potential target in tumors, 41 and a remarkable prognostic marker for multiple human cancers due to its contributions to tumor survival and invasion, 42 , 43 but only one report documented that COPZ1 engages in EV‐A71 replication and interacts directly with the EV‐A71 2C protein. 18 This interaction of host factor with the key viral protein represents a conserved mechanism among different species of enteroviruses, which can be employed to develop broad‐spectrum antivirals for the treatment of enterovirus infections.…”