Unraveling the role of MCM7 in cancer: a comprehensive analysis and functional validation from pan-cancer to lung adenocarcinoma

Background Minichromosome maintenance protein 7 (MCM7), an integral component of the DNA replication licensing complex, has been implicated in diverse human malignancies. However, a holistic, multi-omics evaluation of its oncogenic repertoire across a broad spectrum of cancers remains conspicuously absent. We comprehensively characterized the expression landscape, prognostic significance, genetic aberrations, and immunomodulatory correlations of MCM7 across 33 cancer types, and further experimentally corroborated its functional and mechanistic roles in lung adenocarcinoma (LUAD). Methods We leveraged multi-omics datasets from TCGA, GTEx, CPTAC, and HPA to assess MCM7 expression, survival outcomes, and genomic alterations. Correlative analyses were performed with tumor mutational burden, microsatellite instability, cancer-associated fibroblast infiltration, immune checkpoints, and RNA modification regulators. Functionally, MCM7 was silenced via siRNA in LUAD cell lines, followed by comprehensive assessments of proliferation, cell cycle, migration, invasion, and epithelial-mesenchymal transition. Mechanistic exploration was conducted via RNA-sequencing and western blotting. Results MCM7 is markedly upregulated in most malignant tumors, and its elevated expression is closely associated with poor survival prognosis. Copy number amplification was identified as the predominant genetic alteration, while the R72C/H mutation was specifically linked to dismal outcomes in glioblastoma. Notably, MCM7 expression displayed robust positive correlations with TMB, MSI, the immune checkpoint HMGB1, and the m 5 C reader ALYREF in most cancer types. Functional enrichment reaffirmed its canonical involvement in cell cycle and DNA replication. In vitro , MCM7 knockdown drastically abrogated LUAD cell viability, colony formation, and metastatic capacity, while inducing G0/G1 phase arrest and reversing EMT phenotypes. Mechanistically, transcriptomic and experimental validations convergently revealed that MCM7 silencing exerts its anti-tumor effects via suppression of the JAK-STAT3 signaling cascade. Conclusion Our findings establish MCM7 as a bona fide pan cancer oncogenic determinant and a promising diagnostic/prognostic biomarker. Furthermore, we unveil a novel mechanistic axis linking MCM7 to JAK STAT3 driven inflammatory signaling in LUAD, offering a pre-clinical hypothesis for targeting MCM7 in combination with immunotherapeutic or JAK/STAT inhibitory regimens, although in-vivo validation and toxicity assessment remain essential.