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Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma

BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy that originates from bile duct cells. The incidence and mortality of CCA are very high especially in Southeast Asian countries. Moreover, most CCA patients have a very poor outcome. Presently, there are still no effective treatment regimens for CC...

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Autores principales: Sungwan, Prin, Lert-itthiporn, Worachart, Silsirivanit, Atit, Klinhom-on, Nathakan, Okada, Seiji, Wongkham, Sopit, Seubwai, Wunchana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980698/
https://www.ncbi.nlm.nih.gov/pubmed/33777535
http://dx.doi.org/10.7717/peerj.11067
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author Sungwan, Prin
Lert-itthiporn, Worachart
Silsirivanit, Atit
Klinhom-on, Nathakan
Okada, Seiji
Wongkham, Sopit
Seubwai, Wunchana
author_facet Sungwan, Prin
Lert-itthiporn, Worachart
Silsirivanit, Atit
Klinhom-on, Nathakan
Okada, Seiji
Wongkham, Sopit
Seubwai, Wunchana
author_sort Sungwan, Prin
collection PubMed
description BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy that originates from bile duct cells. The incidence and mortality of CCA are very high especially in Southeast Asian countries. Moreover, most CCA patients have a very poor outcome. Presently, there are still no effective treatment regimens for CCA. The resistance to several standard chemotherapy drugs occurs frequently; thus, searching for a novel effective treatment for CCA is urgently needed. METHODS: In this study, comprehensive bioinformatics analyses for identification of novel target genes for CCA therapy based on three microarray gene expression profiles (GSE26566, GSE32225 and GSE76297) from the Gene Expression Omnibus (GEO) database were performed. Based on differentially expressed genes (DEGs), gene ontology and pathway enrichment analyses were performed. Protein-protein interactions (PPI) and hub gene identifications were analyzed using STRING and Cytoscape software. Then, the expression of candidate genes from bioinformatics analysis was measured in CCA cell lines using real time PCR. Finally, the anti-tumor activity of specific inhibitor against candidate genes were investigated in CCA cell lines cultured under 2-dimensional and 3-dimensional cell culture models. RESULTS: The three microarray datasets exhibited an intersection consisting of 226 DEGs (124 up-regulated and 102 down-regulated genes) in CCA. DEGs were significantly enriched in cell cycle, hemostasis and metabolism pathways according to Reactome pathway analysis. In addition, 20 potential hub genes in CCA were identified using the protein-protein interaction (PPI) network and sub-PPI network analysis. Subsequently, CDC20 was identified as a potential novel targeted drug for CCA based on a drug prioritizing program. In addition, the anti-tumor activity of a potential CDC20 inhibitor, namely dinaciclib, was investigated in CCA cell lines. Dinaciclib demonstrated huge anti-tumor activity better than gemcitabine, the standard chemotherapeutic drug for CCA. CONCLUSION: Using integrated bioinformatics analysis, CDC20 was identified as a novel candidate therapeutic target for CCA.
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spelling pubmed-79806982021-03-26 Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma Sungwan, Prin Lert-itthiporn, Worachart Silsirivanit, Atit Klinhom-on, Nathakan Okada, Seiji Wongkham, Sopit Seubwai, Wunchana PeerJ Bioinformatics BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy that originates from bile duct cells. The incidence and mortality of CCA are very high especially in Southeast Asian countries. Moreover, most CCA patients have a very poor outcome. Presently, there are still no effective treatment regimens for CCA. The resistance to several standard chemotherapy drugs occurs frequently; thus, searching for a novel effective treatment for CCA is urgently needed. METHODS: In this study, comprehensive bioinformatics analyses for identification of novel target genes for CCA therapy based on three microarray gene expression profiles (GSE26566, GSE32225 and GSE76297) from the Gene Expression Omnibus (GEO) database were performed. Based on differentially expressed genes (DEGs), gene ontology and pathway enrichment analyses were performed. Protein-protein interactions (PPI) and hub gene identifications were analyzed using STRING and Cytoscape software. Then, the expression of candidate genes from bioinformatics analysis was measured in CCA cell lines using real time PCR. Finally, the anti-tumor activity of specific inhibitor against candidate genes were investigated in CCA cell lines cultured under 2-dimensional and 3-dimensional cell culture models. RESULTS: The three microarray datasets exhibited an intersection consisting of 226 DEGs (124 up-regulated and 102 down-regulated genes) in CCA. DEGs were significantly enriched in cell cycle, hemostasis and metabolism pathways according to Reactome pathway analysis. In addition, 20 potential hub genes in CCA were identified using the protein-protein interaction (PPI) network and sub-PPI network analysis. Subsequently, CDC20 was identified as a potential novel targeted drug for CCA based on a drug prioritizing program. In addition, the anti-tumor activity of a potential CDC20 inhibitor, namely dinaciclib, was investigated in CCA cell lines. Dinaciclib demonstrated huge anti-tumor activity better than gemcitabine, the standard chemotherapeutic drug for CCA. CONCLUSION: Using integrated bioinformatics analysis, CDC20 was identified as a novel candidate therapeutic target for CCA. PeerJ Inc. 2021-03-17 /pmc/articles/PMC7980698/ /pubmed/33777535 http://dx.doi.org/10.7717/peerj.11067 Text en ©2021 Sungwan et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Sungwan, Prin
Lert-itthiporn, Worachart
Silsirivanit, Atit
Klinhom-on, Nathakan
Okada, Seiji
Wongkham, Sopit
Seubwai, Wunchana
Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma
title Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma
title_full Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma
title_fullStr Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma
title_full_unstemmed Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma
title_short Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma
title_sort bioinformatics analysis identified cdc20 as a potential drug target for cholangiocarcinoma
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980698/
https://www.ncbi.nlm.nih.gov/pubmed/33777535
http://dx.doi.org/10.7717/peerj.11067
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