CDC45 Promotes Proliferation and Glycolysis in Hepatocellular Carcinoma Cells through ERK1/2 Signaling Pathway

Abstract

Background: Cell division cycle protein 45 (CDC45) has been proven to regulate the occurrence and progression of various types of tumors. Therefore, a study was designed to investigate the impact of CDC45 on hepatocellular carcinoma (HCC) and to provide new insights into the novel therapeutic options. Methods: The CDC45 expression level in HCC patients and the overall survival rate of HCC patients with different CDC45 expression levels were analyzed using the starBase and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The HCC cells were transfected with CDC45 overexpression plasmid or siRNA and phosphofructokinase liver type (PFKL) overexpression plasmid, followed by treatment with U0126, an inhibitor of extracellular regulated kinase 1/2 (ERK1/2). The levels of cleaved Caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), and ERK1/2 proteins were measured through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The pyruvate and lactate production, and glucose consumption in HCC cells were determined using their corresponding kits. Additionally, HCC cells were assessed for their viability, number of clones formation, and apoptosis rate using cell function assays. Results: It was found that HCC patients with high CDC45 expression had a shorter survival time. Furthermore, CDC45 overexpression in HCC cells promotes viability, proliferation, and ERK1/2 phosphorylation level while inhibiting the apoptosis (p < 0.05). However, CDC45 silencing has opposite effect and reduces the impacts of PFKL overexpression on HCC cell proliferation and apoptosis (p < 0.001). Moreover, CDC45 overexpression promotes pyruvate and lactate production, and glucose consumption (p < 0.001). However, the U0126 treatment neutralizes the impacts of CDC45 overexpression on cell glycolysis, proliferation, and apoptosis (p < 0.001). Conclusions: It is suggested that CDC45 promotes HCC cell proliferation and glycolysis through ERK1/2 signaling pathway.