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Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapidly lethal tumors. However, limited advances have been made to prolong the survival and to reduce the mortality over the last decades. Therefore, identifying the master regulators underlying ATC progression is desperately neede...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512074/ https://www.ncbi.nlm.nih.gov/pubmed/31183379 http://dx.doi.org/10.1155/2019/9734576 |
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author | Pan, Zongfu Li, Lu Fang, Qilu Qian, Yangyang Zhang, Yiwen Zhu, Junfeng Ge, Minghua Huang, Ping |
author_facet | Pan, Zongfu Li, Lu Fang, Qilu Qian, Yangyang Zhang, Yiwen Zhu, Junfeng Ge, Minghua Huang, Ping |
author_sort | Pan, Zongfu |
collection | PubMed |
description | Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapidly lethal tumors. However, limited advances have been made to prolong the survival and to reduce the mortality over the last decades. Therefore, identifying the master regulators underlying ATC progression is desperately needed. In our present study, three datasets including GSE33630, GSE29265, and GSE65144 were retrieved from Gene Expression Omnibus with a total of 32 ATC samples and 78 normal thyroid tissues. A total of 1804 consistently changed differentially expressed genes (DEGs) were identified from three datasets. KEGG pathways enrichment suggested that upregulated DEGs were mainly enriched in ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, focal adhesion, and p53 signaling pathway. Furthermore, key gene modules in PPI network were identified by Cytoscape plugin MCODE and they were mainly associated with DNA replication, cell cycle process, collagen fibril organization, and regulation of leukocyte migration. Additionally, TOP2A, CDK1, CCNB1, VEGFA, BIRC5, MAPK1, CCNA2, MAD2L1, CDC20, and BUB1 were identified as hub genes of the PPI network. Interestingly, module analysis showed that 8 out of 10 hub genes participated in Module 1 network and more than 70% genes of Module 2 consisted of collagen family members. Notably, transcription factors (TFs) regulatory network analysis indicated that E2F7, FOXM1, and NFYB were master regulators of Module 1, while CREB3L1 was the master regulator of Module 2. Experimental validation showed that CREB3L1, E2F7, and FOXM1 were significantly upregulated in ATC tissue and cell line when compared with normal thyroid group. In conclusion, the TFs regulatory network provided a more detail molecular mechanism underlying ATC occurrence and progression. TFs including E2F7, FOXM1, CREB3L1, and NFYB were likely to be master regulators of ATC progression, suggesting their potential role as molecular therapeutic targets in ATC treatment. |
format | Online Article Text |
id | pubmed-6512074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-65120742019-06-10 Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma Pan, Zongfu Li, Lu Fang, Qilu Qian, Yangyang Zhang, Yiwen Zhu, Junfeng Ge, Minghua Huang, Ping Biomed Res Int Research Article Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapidly lethal tumors. However, limited advances have been made to prolong the survival and to reduce the mortality over the last decades. Therefore, identifying the master regulators underlying ATC progression is desperately needed. In our present study, three datasets including GSE33630, GSE29265, and GSE65144 were retrieved from Gene Expression Omnibus with a total of 32 ATC samples and 78 normal thyroid tissues. A total of 1804 consistently changed differentially expressed genes (DEGs) were identified from three datasets. KEGG pathways enrichment suggested that upregulated DEGs were mainly enriched in ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, focal adhesion, and p53 signaling pathway. Furthermore, key gene modules in PPI network were identified by Cytoscape plugin MCODE and they were mainly associated with DNA replication, cell cycle process, collagen fibril organization, and regulation of leukocyte migration. Additionally, TOP2A, CDK1, CCNB1, VEGFA, BIRC5, MAPK1, CCNA2, MAD2L1, CDC20, and BUB1 were identified as hub genes of the PPI network. Interestingly, module analysis showed that 8 out of 10 hub genes participated in Module 1 network and more than 70% genes of Module 2 consisted of collagen family members. Notably, transcription factors (TFs) regulatory network analysis indicated that E2F7, FOXM1, and NFYB were master regulators of Module 1, while CREB3L1 was the master regulator of Module 2. Experimental validation showed that CREB3L1, E2F7, and FOXM1 were significantly upregulated in ATC tissue and cell line when compared with normal thyroid group. In conclusion, the TFs regulatory network provided a more detail molecular mechanism underlying ATC occurrence and progression. TFs including E2F7, FOXM1, CREB3L1, and NFYB were likely to be master regulators of ATC progression, suggesting their potential role as molecular therapeutic targets in ATC treatment. Hindawi 2019-04-28 /pmc/articles/PMC6512074/ /pubmed/31183379 http://dx.doi.org/10.1155/2019/9734576 Text en Copyright © 2019 Zongfu Pan et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Pan, Zongfu Li, Lu Fang, Qilu Qian, Yangyang Zhang, Yiwen Zhu, Junfeng Ge, Minghua Huang, Ping Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma |
title | Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma |
title_full | Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma |
title_fullStr | Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma |
title_full_unstemmed | Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma |
title_short | Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma |
title_sort | integrated bioinformatics analysis of master regulators in anaplastic thyroid carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512074/ https://www.ncbi.nlm.nih.gov/pubmed/31183379 http://dx.doi.org/10.1155/2019/9734576 |
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