CBX3 is associated with metastasis and glutathione/glycosphingolipid metabolism in colon adenocarcinoma

Abstract

Metastasis is the major cause of colon adenocarcinoma (COAD) mortality. Increasing studies demonstrated that the epigenetics and downstream expression change of pivotal genes may act as a major role in promoting COAD progression and metastasis. Therefore, identifying the dysregulation of key genes associating with COAD metastasis may provide a new strategy for the discovery of potential treatment targets. This study included a single-cell RNA sequencing profile consisting of 17,469 tumor cells derived from 23 samples, and 326 COADs available from The Cancer Genome Atlas (TCGA), etc. The study was performed using comparative analysis to characterize the role of CBX3 in COAD metastasis and progression. This study revealed that the mRNA level of Chromebox homolog 3 (CBX3) in the metastatic COAD was significantly higher than that of the primary COAD and normal colon tissues (Wilcoxon's rank-sum test, P<0.05). Activation of CBX3 was involved in regulating an interaction network consisting of CCT6A, LSM5, and GGCT, etc., which may subsequently participate in glutathione metabolism. Besides, CBX3 also exhibited a negative correlation with glycosphingolipid metabolism, which may associate with the regulation of CBX3 on DNA methylation. Clinical data analysis demonstrated that patients with high CBX3 mRNA levels showed a nearly 2-fold shorter overall survival time than the control group (hazard ratio =1.59; likelihood ratio test, P=0.04). Our study demonstrated that CBX3 overexpression is associated with COAD metastasis. CBX3 downstream regulation network involves in TCP1 complex, LSM family, and glutathione metabolism, which may provide a potential target for suppressing tumor metastasis.