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Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis

Metastasis is the leading cause of melanoma-related mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. This study aimed to screen the core genes and molecular mechanisms related to melanom...

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Autores principales: Xie, Renjian, Li, Bifei, Jia, Lee, Li, Yumei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775799/
https://www.ncbi.nlm.nih.gov/pubmed/35054979
http://dx.doi.org/10.3390/ijms23020794
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author Xie, Renjian
Li, Bifei
Jia, Lee
Li, Yumei
author_facet Xie, Renjian
Li, Bifei
Jia, Lee
Li, Yumei
author_sort Xie, Renjian
collection PubMed
description Metastasis is the leading cause of melanoma-related mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. 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.
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spelling pubmed-87757992022-01-21 Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis Xie, Renjian Li, Bifei Jia, Lee Li, Yumei Int J Mol Sci Article Metastasis is the leading cause of melanoma-related mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. 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. MDPI 2022-01-12 /pmc/articles/PMC8775799/ /pubmed/35054979 http://dx.doi.org/10.3390/ijms23020794 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xie, Renjian
Li, Bifei
Jia, Lee
Li, Yumei
Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis
title Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis
title_full Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis
title_fullStr Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis
title_full_unstemmed Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis
title_short Identification of Core Genes and Pathways in Melanoma Metastasis via Bioinformatics Analysis
title_sort identification of core genes and pathways in melanoma metastasis via bioinformatics analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775799/
https://www.ncbi.nlm.nih.gov/pubmed/35054979
http://dx.doi.org/10.3390/ijms23020794
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AT jialee identificationofcoregenesandpathwaysinmelanomametastasisviabioinformaticsanalysis
AT liyumei identificationofcoregenesandpathwaysinmelanomametastasisviabioinformaticsanalysis