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Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma
Esophageal squamous cell carcinoma (ESCC), the main subtype of esophageal cancer (EC), is a common lethal type of cancer with a high mortality rate. The aim of the present study was to select key relevant genes and identify potential mechanisms involved in the development of ESCC based on bioinforma...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388536/ https://www.ncbi.nlm.nih.gov/pubmed/32583000 http://dx.doi.org/10.3892/or.2020.7658 |
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author | Li, Xuebing Ren, Zhenzhen Xiong, Chao Geng, Jie Li, Yuqing Liu, Cong Ren, Chunfeng Liu, Hongchun |
author_facet | Li, Xuebing Ren, Zhenzhen Xiong, Chao Geng, Jie Li, Yuqing Liu, Cong Ren, Chunfeng Liu, Hongchun |
author_sort | Li, Xuebing |
collection | PubMed |
description | Esophageal squamous cell carcinoma (ESCC), the main subtype of esophageal cancer (EC), is a common lethal type of cancer with a high mortality rate. The aim of the present study was to select key relevant genes and identify potential mechanisms involved in the development of ESCC based on bioinformatics analysis. Minichromosome maintenance 6 complex component (MCM6) has been identified to be upregulated in multiple malignancies; however, its contributions to ESCC remain unclear. For the purposes of the present study, four datasets were downloaded from the Gene Expression Omnibus (GSE63941, GSE26886, GSE17351 and GSE77861), and the intersection of the differentially expressed genes was obtained using a Venn diagram. The protein-protein interaction was then constructed, and the modules were verified by Cytoscape, in which the key genes have a high connectivity degree with other genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were subsequently filtered out to analyze the development of ESCC. MCM6, an upregulated gene, was selected and connected with most of the other genes, for further research validation. The expression levels of MCM6 were then assessed using the Oncomine, GEPIA and UALCAN databases and validated in both ESCC tissues samples and cell lines by immunohistochemistry and RT-qPCR. Cell counting kit-8 (CCK-8), flow cytometry, wound healing and Transwell assays were used to determine the proliferation, apoptosis, cell cycle, migration and invasion of ESCC cells. A total of 24 genes were identified by a series of bioinformatics analyses and the results revealed that the genes were associated with DNA replication and cell cycle. Experimental validation revealed that MCM6 expression was significantly elevated in both ESCC tissues and cell lines. The results were consistent with those of bioinformatics analysis. Furthermore, the knockdown of MCM6 inhibited cell proliferation, migration and invasion and promoted cell apoptosis, and made cells arrested in S stage. In summary, the findings of bioinformatics analysis provided a novel hypothesis for ESCC progression. In particular, the aberrantly elevated expression of MCM6 is a potential biomarker for ESCC diagnosis and treatment. |
format | Online Article Text |
id | pubmed-7388536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-73885362020-08-05 Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma Li, Xuebing Ren, Zhenzhen Xiong, Chao Geng, Jie Li, Yuqing Liu, Cong Ren, Chunfeng Liu, Hongchun Oncol Rep Articles Esophageal squamous cell carcinoma (ESCC), the main subtype of esophageal cancer (EC), is a common lethal type of cancer with a high mortality rate. The aim of the present study was to select key relevant genes and identify potential mechanisms involved in the development of ESCC based on bioinformatics analysis. Minichromosome maintenance 6 complex component (MCM6) has been identified to be upregulated in multiple malignancies; however, its contributions to ESCC remain unclear. For the purposes of the present study, four datasets were downloaded from the Gene Expression Omnibus (GSE63941, GSE26886, GSE17351 and GSE77861), and the intersection of the differentially expressed genes was obtained using a Venn diagram. The protein-protein interaction was then constructed, and the modules were verified by Cytoscape, in which the key genes have a high connectivity degree with other genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were subsequently filtered out to analyze the development of ESCC. MCM6, an upregulated gene, was selected and connected with most of the other genes, for further research validation. The expression levels of MCM6 were then assessed using the Oncomine, GEPIA and UALCAN databases and validated in both ESCC tissues samples and cell lines by immunohistochemistry and RT-qPCR. Cell counting kit-8 (CCK-8), flow cytometry, wound healing and Transwell assays were used to determine the proliferation, apoptosis, cell cycle, migration and invasion of ESCC cells. A total of 24 genes were identified by a series of bioinformatics analyses and the results revealed that the genes were associated with DNA replication and cell cycle. Experimental validation revealed that MCM6 expression was significantly elevated in both ESCC tissues and cell lines. The results were consistent with those of bioinformatics analysis. Furthermore, the knockdown of MCM6 inhibited cell proliferation, migration and invasion and promoted cell apoptosis, and made cells arrested in S stage. In summary, the findings of bioinformatics analysis provided a novel hypothesis for ESCC progression. In particular, the aberrantly elevated expression of MCM6 is a potential biomarker for ESCC diagnosis and treatment. D.A. Spandidos 2020-09 2020-06-23 /pmc/articles/PMC7388536/ /pubmed/32583000 http://dx.doi.org/10.3892/or.2020.7658 Text en Copyright: © Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Li, Xuebing Ren, Zhenzhen Xiong, Chao Geng, Jie Li, Yuqing Liu, Cong Ren, Chunfeng Liu, Hongchun Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma |
title | Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma |
title_full | Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma |
title_fullStr | Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma |
title_full_unstemmed | Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma |
title_short | Minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma |
title_sort | minichromosome maintenance 6 complex component identified by bioinformatics analysis and experimental validation in esophageal squamous cell carcinoma |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388536/ https://www.ncbi.nlm.nih.gov/pubmed/32583000 http://dx.doi.org/10.3892/or.2020.7658 |
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