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pmid:35054979
Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis.
Renjian Xie · Bifei Li · Lee Jia · Yumei Li
International journal of molecular sciences · 2022 doi:10.3390/ijms23020794
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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This study aimed to screen the core genes and molecular mechanisms related to melanoma metastasis. A gene expression profile, GSE8401, including 31 primary melanoma and 52 metastatic melanoma clinical samples, was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between melanoma metastases and primary melanoma were screened using GEO2R tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses of DEGs were performed using the Database for Annotation Visualization and Integrated Discovery (DAVID). The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape with Molecular Complex Detection (MCODE) plug-in tools were utilized to detect the protein-protein interaction (PPI) network among DEGs. The top 10 genes with the highest degrees of the PPI network were defined as hub genes. In the results, 425 DEGs, including 60 upregulated genes and 365 downregulated genes, were identified. The upregulated genes were enriched in ECM-receptor interactions and the regulation of actin cytoskeleton, while 365 downregulated genes were enriched in amoebiasis, melanogenesis, and ECM-receptor interactions. The defined hub genes included CDK1, COL17A1, EGFR, DSG1, KRT14, FLG, CDH1, DSP, IVL, and KRT5. In addition, the mRNA and protein levels of the hub genes during melanoma metastasis were verified in the TCGA database and paired post- and premetastatic melanoma cells, respectively. Finally, KRT5-specific siRNAs were utilized to reduce the KRT5 expression in melanoma A375 cells. An MTT assay and a colony formation assay showed that KRT5 knockdown significantly promoted the proliferation of A375 cells. A Transwell assay further suggested that KRT5 knockdown significantly increased the cell migration and cell invasion of A375 cells. This bioinformatics study provided a deeper understanding of the molecular mechanisms of melanoma metastasis. The in vitro experiments showed that KRT5 played the inhibitory effects on melanoma metastasis. Therefore, KRT5 may serve important roles in melanoma metastasis.", "claims": [{"id": "claim-method", "statement": "The adjusted p-value was calculated to reduce the false positive rate, applying the Benjamini and Hochberg false discovery rate method by default. Genes within the cutoff criteria of an adjusted p-value < 0.05 and |log2 (Fold change)| ≥ 1.5 were designated DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35054979", "locator": "sections[12] \"4.2. Identification of the DEGs\" paragraph 2", "quote": "The adjusted p-value was calculated to reduce the false positive rate, applying the Benjamini and Hochberg false discovery rate method by default. 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After 7 weeks, all mice were sacrificed, and the pulmonary metastatic nodules were s", "l Inc., Shanghai, China). After 7 weeks, all mice were sacrificed, and the pulmonary metastatic nod", "(3 × 105 cells in 0.1 mL saline solution per mouse) were intravenously injected into the tails"], "order_basis": "paper_text_order:2937", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ization. Subsequently, these monoplasts were cultured in vitro to establish the A375M cell line. The", "ll line. The cell lines mentioned above were cultured in RPMI 1640 medium (HyClone, Logan, UT, USA) s", "ization. Subsequently, these monoplasts were cultured in vitro to establish the A375M cell line. 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