Overexpression of MCM3 as a prognostic biomarker correlated with cell proliferation, cell cycle and immune regulation in hepatocellular carcinoma.

Abstract

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor and has a poor prognosis. Minichromosome maintenance 3 (MCM3) protein is upregulated in several cancers, but the biological function, molecular mechanisms and the relationship with tumor immunity of MCM3 in HCC remain poorly understood. Methods: The expression levels and prognosis role of MCM3 in HCC were analyzed based on TCGA, GEO and LIHC databases, and 40 paired tissue samples. We conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses on these DEGs to explore the potential impact of MCM3 on the biological behavior of HCC. In addition, flow cytometry, CCK-8, EdU, colony formation and nude mice xenograft models were employed to investigate the biological functions of MCM3. Furthermore, immune cell infiltration, markers and checkpoint-associated genes were analyzed by TIMER 2.0, ACLBI and TCGA database. Results: In this study, we investigated the expression and function of MCM3 in HCC. MCM3 was highly expressed in a variety of tumors including HCC, and high MCM3 expression was positively associated with various clinicopathological parameters and acted as an independent factor of the poor prognosis for overall survival in HCC. Meanwhile, immune characteristics analysis indicated that high MCM3 expression was related to the level of immune cell infiltration and immune checkpoints in HCC. Our functional enrichment analysis indicated that MCM3 is mainly involved in the cell cycle and cell metabolic related pathways. Moreover, in vitro and in vivo experiments further confirmed that MCM3 could promote the proliferation of HCC by regulating cell cycle progression. Conclusions: Our results indicated that MCM3 was up-regulated in HCC and might become a biomarker in the diagnosis and treatment of patients with HCC.