CT23 knockdown attenuating malignant behaviors of hepatocellular carcinoma cell is associated with upregulation of metallothionein 1

Abstract

The cancer‐testis antigen 23 (CT23) gene has been reported in association with the pathogenesis and progress of hepatocellular carcinoma (HCC). However, the alterations of gene expression profiling induced by CT23 knockdown in HCC cells remains largely unknown. In this study, the RNA interfering (RNAi) method was used to silence CT23 expression in BEL‐7404 cells. Microarray analysis was performed on mRNA extracted from the CT23 knockdown cells and the control cells to determine the alterations of gene expression profiles. The result showed a total of 1051 genes expressed differentially (two‐fold change), including 470 genes upregulated and 581 gene downregulated in the CT23 knockdown cells. A bioinformatic analysis showed that the functional differentially expressed genes (DEGs) were linked to cell proliferation, migration, and apoptosis, and metallothionein 1 (MT1) attained the maximum enrichment scores in functional annotation, classification, and pathway analysis of DEGs. Furthermore, Western blot analysis and cell behaviors assays verified that CT23 modulates cell proliferation, migration, and apoptosis by regulating MT1 expression in HCC cells and non‐neoplastic hepatocytes. In summary, downregulated CT23 gene in BEL‐7404 cells might change the expressions of carcinogenesis and progression related genes in HCC by upregulating MT1 expression, which would provide insight into searching for a novel therapeutic target for HCC.

Integrating the Epigenome and Transcriptome of Hepatocellular Carcinoma to Identify Systematic Enhancer Aberrations and Establish an Aberrant Enhancer-Related Prognostic Signature

“…As mentioned earlier, nine identified DEE-associated differentially expressed MT isoforms were reported to be involved in liver cancer. Specifically, the upregulation of MT1A mediated the attenuation of malignant behaviors of CT23 knockdown in HCC cells ( Ning et al, 2021 ). MT1DP is a pivotal anticancer long noncoding RNA (lncRNA), whose suppression mediates the vital carcinogenetic roles of RUNX2 and YAP in HCC ( Yu et al, 2014a ).…”

Prediction and identification of HLA-A*0201-restricted epitopes from cancer testis antigen CT23

“… 10 Some of experiments in vitro have confirmed that down-regulating CT23 can reduce cancer cell growth, prevent cancer cell migration and invasion, and elevate the expression of apoptosis-related proteins, thereby promoting cell apoptosis. 11 , 12 In patients with ovarian cancer, high expression of CT23 was associated with paclitaxel resistance, stage and chemotherapy sensitivity, shortened survival time and accelerated recurrence rate, 10 , 13 while in colorectal cancer patients, high expression of CT23 is also confirmed to be correlated with tumor invasion stage and histological grade. 15 Furthermore, the presence of CT23 antibodies in the serum of patients with various tumors, including ovarian cancer, colorectal cancer, liver cancer, and glioma, indicates that CT23 is immunogenic and can induce a specific immune response, 13–15 , 17 making it a potential diagnostic and therapeutic target in cancer.…”