MCM6 Promotes Hepatocellular Carcinoma Progression via the Notch Pathway: Clinical, Functional, and Genomic Insights.

ABSTRACT

Objective: To evaluate the expression profile of MCM6 in HCC and the relationship between MCM6 level and clinicopathological parameters through bioinformatics analysis of several databases. Methods: MCM expression level, clinical parameters, survival data, and gene set enrichment analysis were analyzed by bioinformatics database, including Oncomine™, UALCAN, HCCDB, TCGA, cBioPortal, and LinkedOmics. Real-time PCR, western blotting, and IHC staining were conducted to identify the expression of MCM6 in HCC compared to normal liver tissues. Results: Bioinformatics analysis indicated that the mRNA of MCM6 was obviously increased in multiple cancer types, especially in HCC. MCM6 level was positively associated with multiple clinical parameters (stage 3 and grades 3 and 4) and negatively associated with patient outcomes (overall survival). Moreover, enrichment of functions and signaling pathways analysis of MCM6 suggested that MCM6 might mediate DNA replication and cellular metabolism to promote the development and progression of HCC. Furthermore, IHC staining and western blotting indicated that the MCM6 was enhanced in HCC tissue, and MCM6 could promote HCC proliferation in activating Notch pathway via WB and bioinformatic analysis. Conclusion: This study actually revealed the expression and related functions of MCM6 in HCC. Furthermore, MCM6 is a carcinogenic role in activating Notch pathway to promote HCC cell proliferation, which may be a new prognostic biomarker and therapeutic target for HCC patients.