MCM8 promotes NR4A1-mediated E2F1 transcription and facilitates renal cell carcinoma through enhancing aerobic glycolysis.

Abstract

Renal cell carcinoma (RCC) is a type of renal malignancy originated from the urinary tubular epithelial system. Despite its high incidence, the molecular mechanisms driving its pathogenesis remain poorly understood, limiting therapeutic advancements. This study explored the link between MCM8 and RCC progression. MCM8 displays significantly high expression in RCC tissues and was closely associated with RCC pathological staging. Knocking down endogenous MCM8 in RCC cells significantly suppressed malignant phenotypes, while simultaneously inducing apoptosis. Similarly, in vivo experiments confirmed these findings, showing a pronounced reduction in tumor growth upon MCM8 silencing. Mechanistic investigations revealed that MCM8 regulates E2F1 expression by interacting with the transcription factor NR4A1, thereby affecting E2F1 transcriptional activity. Additionally, MCM8 and E2F1 collaboratively influence aerobic glycolysis and the cellular behavior of RCC cells. In conclusion, this study identifies MCM8 as a tumor-promoting factor in RCC, with its oncogenic role potentially mediated by its regulation of E2F1 expression.