Mcm4, a member of the minichromosome maintenance (MCM) protein family, forms the pre-replication complex (MCM2-7) with other MCM proteins. This complex binds to replication origins at the G1 stage of the cell cycle, playing a crucial role in DNA replication initiation. It is also involved in cell cycle progression and has been associated with multiple signaling pathways relevant to cancer development [2].

In cancer research, MCM4 has emerged as a significant biomarker and potential therapeutic target. In hepatocellular carcinoma (HCC), MCM4 is upregulated, and its inhibition enhances the efficacy of sorafenib by promoting ferroptosis, potentially through Nrf2 signaling pathway activation although no direct interaction was found between Nrf2 and MCM4 [1]. In lung adenocarcinoma (LUAD), MCM4 is highly expressed, promoting cell proliferation and suppressing apoptosis. Knockdown of MCM4 in a xenograft mouse model inhibited tumor growth and caused cell cycle arrest at the G1 stage [2]. In urothelial carcinoma (UC), strong nuclear expression of MCM4 in tissues was associated with high-grade histology, high T stage, and poor prognosis, and MCM4 immunostaining improved the diagnostic accuracy of urine cytology [3]. In malignant melanoma, MCM4 promotes tumor growth and metastasis by activating the PI3K/AKT pathway [4]. In soft-tissue sarcoma, MCM4 is associated with genomic instability, BRCAness phenotype, and tumors with MCM4 overexpression are sensitive to PARP inhibitor and platinum chemotherapy [5]. In glioma, MCM4 is a prognostic biomarker and promotes cancer cell growth [6].

In conclusion, MCM4 is essential for DNA replication and cell cycle regulation. Model-based research, especially in cancer, has revealed its role as a biomarker and potential therapeutic target in various malignancies including HCC, LUAD, UC, malignant melanoma, soft-tissue sarcoma, and glioma. Understanding MCM4's function provides insights into disease mechanisms and possible treatment strategies.