System analysis identifies UBE2C as a novel oncogene target for adrenocortical carcinoma

Abstract

Ubiquitin Conjugating Enzyme 2C (UBE2C) is an emerging target gene for tumor progression. However, the tumorigenic effect and mechanism of UBE2C in adrenocortical carcinoma (ACC) remains unclear. Systematic investigation of the tumorigenic effect of UBE2C may help in understanding its prognostic value in adrenocortical carcinoma. First, we exploited the intersection on DFS-related genes, OS-related genes, highly expressed genes in adrenocortical carcinoma as well as differentially expressed genes (DEGs) between tumor and normal, and then obtained 20 candidate genes. UBE2C was identified to be the most significant DEG between tumor and normal. It is confirmed that high expression of UBE2C was strongly associated with poor prognosis in patients with ACC by analyzing RNA-seq data of ACC obtained from the Cancer Genome Atlas (TCGA) database implemented by ACLBI Web-based Tools. UBE2C expression could also promote m6A modification and stemness in ACC. We found that UBE2C expression is positively associated with the expression of CDC20, CDK1, and CCNA2 using ACLBI Web-based Tools, indicated the hyperactive cell cycle progression present in ACC with high UBE2C expression. In addition, UBE2C knockdown could significantly inhibit the proliferation, migration, invasion, EMT of adrenocortical carcinoma cells as well as the cell cycle progression in vitro. Notably, pan-cancer analysis also identified UBE2C as an oncogene in various tumors. Taken together, UBE2C was strongly associated with poor prognosis of patients with ACC by promoting cell cycle progression and EMT. This study provides a new theoretical basis for the development of UBE2C as a molecular target for the treatment of ACC.

Ubiquitin-conjugating enzyme 2C (UBE2C) plays as a cancer diagnostic and prognostic marker: A Bioinformatics pan-cancer analysis

“…Furthermore, the correlation of UBE2C expression with clinical outcomes con rmed that UBE2C overexpression results in poor prognosis, worse overall survival, and disease-free survival in many cancers. These results were in agreement with previous ndings in adrenocortical and oral squamous cell carcinoma (45,48). Recent studies showed that the high expression of UBE2C has correlation with poor OS and DFS of cancer patients (44,45,46,47).…”

“…These results were in agreement with previous ndings in adrenocortical and oral squamous cell carcinoma (45,48). Recent studies showed that the high expression of UBE2C has correlation with poor OS and DFS of cancer patients (44,45,46,47). Similarly, according to our study, the high expression of UBE2C was signi cantly correlated with poor prognosis and shorter OS of patients with ACC, BRCA, KIRC, KIRP, LGG, LUAD, MESO, PAAD, and SKCM.…”

“…Furthermore, in our study, the expression level of UBE2C has altered in different pathological stages which positively correlated with cancer stage and the results showed higher expression of UBE2C in the late stages of cancer compared to early stages including ACC, BRCA, KICH, KIRC, KIRP, LIHC, LUAD, LUSC, PAAD, TGCT, and THCA. Previous studies showed that the UBE2C expression level involved in cancer progression and invasion (44,45,46,47). As well, the result showed that signi cant high protein expression levels of UBE2C protein in 20 different cancer type increase.…”

Role of UBE2C in Brain Cancer Invasion and Dissemination

“…This effect has also been demonstrated in renal, prostate, and gastric cancers [94][95][96]. Recently, Huang et al proposed that patients with adrenocortical carcinoma with high UBE2C expression may present a worse prognosis by inducing self-renewal of adrenocortical stem cells [73].…”

“…In addition, several immune checkpoint genes exhibit a positive correlation with UBE2C [74]. Other studies have reported a correlation between UBE2C and immune cell infiltration [61,69,72,73,102]. Specifically in hepatocellular carcinoma, UBE2C is positively correlated with infiltration of regulatory T cells and T follicular helper cells while presenting a negative correlation with macrophage infiltration [69].…”