CDCA5, Transcribed by E2F1, Promotes Oncogenesis by Enhancing Cell Proliferation and Inhibiting Apoptosis via the AKT Pathway in Hepatocellular Carcinoma

Abstract

Cell division cycle associated 5 (CDCA5) is an important element for the interaction between cohesin and chromatin in interphase. It is abnormally expressed in many types of cancer and works as an indicator of poor prognosis, but little is known about its activity in hepatocellular carcinoma (HCC). In the present study, we found that the expression of CDCA5 was upregulated in HCC tissues compared to paracancerous tissues and had a negative correlation with patient survival. Cell proliferation and tumorigenesis were inhibited and cell apoptosis was induced with the knockdown of CDCA5, suggesting an oncogenic role of CDCA5 in liver cancer. Luciferase reporter assay and chromatin immunoprecipitation showed that CDCA5 was transcribed by E2F1. Furthermore, we confirmed that CDCA5 interrupted cell behavior via the AKT pathway. These findings demonstrated that CDCA5 plays an important role in HCC progression.

Analysis of the Expression of Cell Division Cycle-Associated Genes and Its Prognostic Significance in Human Lung Carcinoma: A Review of the Literature Databases

“…A recent study shows that CDCA5 probably serves as a biomarker for the prognosis, treatment, and diagnosis for HCC [38][39][40]. It also exerts a vital part in the proliferation of HCC cells [41,42], OSCC [41,42], and bladder cancer [43].…”

Increased Expression Together with the Gene Regulation Network of NEIL3 Predicts Poor Prognosis and Correlates with Immune Infiltrates in Hepatocellular Carcinoma

“…Among the TFs targeted by NEIL3, E2F1 represents a key link in the cell cycle regulation network, and its aberrant expression participates in HCC occurrence and development, which also predicts the unfavorable patient prognosis [42]. As reported, E2F1, which is tightly linked to cell division cycle associated 5 (CDCA5), Sirtuin 5 (SIRT5) and other important molecules, may serve as a vital anti-apoptotic factor in liver cancer due to its ability to offset c-Myc-driven apoptosis [43,44]. As suggested in previous literature, the repressive complex, which includes the component of E2F4, is relieved by CDK upon reentry into the cell cycle; thereafter, E2F1-Sp1, which is in the form of complex E2F1-NF-Y, can be recruited to the promoter [45].…”

Identification and Analysis of Genes Associated with Epithelial Ovarian Cancer by Integrated Bioinformatics Methods

“…CDCA5 participated the promotion of HCC cells proliferation, migration, and invasion, palying a tumor-promotive role and being a potential therapeutic target for patients with HCC [16,17]. Besides, CDCA5 was found to be transcribed by E2F1, and could promote oncogenesis by enhancing cell proliferation and inhibiting apoptosis via the AKT pathway in HCC [18]. Another research found that increased CDCA5 expression was associated with increased tumor diameter and microvascular invasion in HCC [19].…”