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pmid:38342795
FOXM1 promote the growth and metastasis of uveal melanoma cells by regulating CDK2 expression.
Xue Bai · Shan Li · Yan Luo
International ophthalmology · 2024 doi:10.1007/s10792-024-02943-y
Paper
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Experiment
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Complete file
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Forkhead box protein M1 (FOXM1) is a transcription factor that regulates the expression of cell cycle-related genes that are necessary for DNA duplication. However, the regulatory mechanism of FOXM1 in UVM was still not clear. Here, we investigated the regulation of FOXM1 in the malignant phenotype of UVM cells and its effect on the prognosis of UVM patients.\nMETHODS: UVM gene expression profiles were obtained using GSE22138 data from the gene expression omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) was used to construct a key module gene for metastasis, which was strongly correlated with UVM prognosis. The latent biological pathways were identified through gene ontology analysis. Protein-protein interaction (PPI) networks and hub shared gene authentication were performed. GEPIA and UALCAN databases were used for the analysis of relationship between candidate genes (FOXM1 or MET) and the prognosis of UVM patients. The abundance of FOXM1 was examined by quantitative real time polymerase chain reaction (qRT-PCR) and western blot. Colony formation and cell counting kit-8 (CCK-8) assays for cell proliferation, wound healing assay for migration, and transwell invasion analysis for invasion were performed.\nRESULTS: GEO database showed the differentially expressed genes between UVM samples with or without metastasis, and a key module gene for metastasis was constructed by WGCNA. The PPI network revealed that seven candidate genes (VEGFA, KRAS, MET, SRC, EZR, FOXM1, and CCNB1) were closely associated with UVM metastasis. GEPIA and UALCAN analyzes suggested that FOXM1 and MET are related to the prognosis of patients with UVM. These experimental results suggested that FOXM1 was highly expressed in UVM cells. FOXM1 deficiency represses the proliferative, migratory, and invasive abilities of UVM cells.\nCONCLUSIONS: FOXM1 silencing may hinder UVM cell progression, providing a novel theoretical basis and new insights for UVM treatment.", "claims": [{"id": "claim-method", "statement": "The limma R package (Version 3.38.3; http://www.bioconductor.org/packages/release/bioc/html/limma.html) was utilized to explore the differentially expressed genes between tumor tissues of “No” group (28 cases) and the “Yes” (35 cases), the threshold was set to: |log2FC|> 0 and P value < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38342795", "locator": "sections[4] \"Weighted gene co-expression network analysis (WGCNA) and functional annotation\" paragraph 2", "quote": "The limma R package (Version 3.38.3; http://www.bioconductor.org/packages/release/bioc/html/limma.html) was utilized to explore the differentially expressed genes between tumor tissues of “No” group (28 cases) and the “Yes” (35 cases), the threshold was set to: |log2FC|> 0 and P value < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile matrix file from GSE22138 based on the platform GPL570 (including transcription profile data of 63 UVM tissue samples and matching clinically relevant information) was acquired from the gene expression omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). 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