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Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma

BACKGROUND: Gallbladder carcinoma (GBC) is a highly malignant tumor with a poor overall prognosis. This study aimed to identify the characteristic microRNAs (miRNAs) of GBC and the competing endogenous RNA (ceRNA) regulatory mechanisms. METHODS: The microarray data of GBC tissue samples and normal g...

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Autores principales: Shao, Hanrui, Zhu, Jiahai, Zhu, Ya, Liu, Lixin, Zhao, Songling, Kang, Qiang, Liu, Yunxia, Zou, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10566037/
https://www.ncbi.nlm.nih.gov/pubmed/37821907
http://dx.doi.org/10.1186/s12920-023-01663-z
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author Shao, Hanrui
Zhu, Jiahai
Zhu, Ya
Liu, Lixin
Zhao, Songling
Kang, Qiang
Liu, Yunxia
Zou, Hao
author_facet Shao, Hanrui
Zhu, Jiahai
Zhu, Ya
Liu, Lixin
Zhao, Songling
Kang, Qiang
Liu, Yunxia
Zou, Hao
author_sort Shao, Hanrui
collection PubMed
description BACKGROUND: Gallbladder carcinoma (GBC) is a highly malignant tumor with a poor overall prognosis. This study aimed to identify the characteristic microRNAs (miRNAs) of GBC and the competing endogenous RNA (ceRNA) regulatory mechanisms. METHODS: The microarray data of GBC tissue samples and normal gallbladder (NGB) tissue samples from the Gene Expression Omnibus (GEO) database was downloaded. GBC-related differentially expressed miRNAs (DE-miRNAs) were identified by inter-group differential expression analysis and weighted gene co-expression network analysis (WGCNA). Machine learning algorithms were used to screen the characteristic miRNA based on the intersect between least absolute shrinkage and selection operator (LASSO) and Support vector machine-recursive feature elimination (SVM-RFE). Based on the differential expression analysis of GEO database, the ceRNA network of characteristic miRNA was predicted and constructed. The biological functions of the ceRNA network were revealed by carrying out the gene enrichment analysis was implemented. We further screened the key genes of ceRNA network and constructed a protein-protein interaction (PPI) network, and predicted and generated the transcription factors (TFs) network of signature miRNAs. The expression of characteristic miRNA in clinical samples was verified by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 131 GBC-related DE-miRNAs were obtained. The hsa-miR-4770 was defined as characteristic miRNA for GBC. The ceRNA network containing 211 mRNAs, one miRNA, two lncRNAs, and 48 circRNAs was created. Gene enrichment analysis suggested that the downstream genes were mainly involved in actin filament organization, cell-substrate adhesion, cell-matrix adhesion, reactive oxygen species metabolic process, glutamine metabolic process and extracellular matrix (ECM)-receptor interaction pathway. 10 key genes in the network were found to be most correlated with disease, and involved in cell cycle-related processes, p53, and extrinsic apoptotic signaling pathways. The qRT-PCR result demonstrated that hsa-miR-4770 is down-regulated in GBC, and the expression trend is consistent with the public database. CONCLUSIONS: We identified hsa-miR-4770 as the characteristic miRNA for GBC. The ceRNA network of hsa-miR-4770 may play key roles in GBC. This study provided some basis for potential pathogenesis of GBC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01663-z.
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spelling pubmed-105660372023-10-12 Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma Shao, Hanrui Zhu, Jiahai Zhu, Ya Liu, Lixin Zhao, Songling Kang, Qiang Liu, Yunxia Zou, Hao BMC Med Genomics Research BACKGROUND: Gallbladder carcinoma (GBC) is a highly malignant tumor with a poor overall prognosis. This study aimed to identify the characteristic microRNAs (miRNAs) of GBC and the competing endogenous RNA (ceRNA) regulatory mechanisms. METHODS: The microarray data of GBC tissue samples and normal gallbladder (NGB) tissue samples from the Gene Expression Omnibus (GEO) database was downloaded. GBC-related differentially expressed miRNAs (DE-miRNAs) were identified by inter-group differential expression analysis and weighted gene co-expression network analysis (WGCNA). Machine learning algorithms were used to screen the characteristic miRNA based on the intersect between least absolute shrinkage and selection operator (LASSO) and Support vector machine-recursive feature elimination (SVM-RFE). Based on the differential expression analysis of GEO database, the ceRNA network of characteristic miRNA was predicted and constructed. The biological functions of the ceRNA network were revealed by carrying out the gene enrichment analysis was implemented. We further screened the key genes of ceRNA network and constructed a protein-protein interaction (PPI) network, and predicted and generated the transcription factors (TFs) network of signature miRNAs. The expression of characteristic miRNA in clinical samples was verified by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 131 GBC-related DE-miRNAs were obtained. The hsa-miR-4770 was defined as characteristic miRNA for GBC. The ceRNA network containing 211 mRNAs, one miRNA, two lncRNAs, and 48 circRNAs was created. Gene enrichment analysis suggested that the downstream genes were mainly involved in actin filament organization, cell-substrate adhesion, cell-matrix adhesion, reactive oxygen species metabolic process, glutamine metabolic process and extracellular matrix (ECM)-receptor interaction pathway. 10 key genes in the network were found to be most correlated with disease, and involved in cell cycle-related processes, p53, and extrinsic apoptotic signaling pathways. The qRT-PCR result demonstrated that hsa-miR-4770 is down-regulated in GBC, and the expression trend is consistent with the public database. CONCLUSIONS: We identified hsa-miR-4770 as the characteristic miRNA for GBC. The ceRNA network of hsa-miR-4770 may play key roles in GBC. This study provided some basis for potential pathogenesis of GBC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01663-z. BioMed Central 2023-10-11 /pmc/articles/PMC10566037/ /pubmed/37821907 http://dx.doi.org/10.1186/s12920-023-01663-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Shao, Hanrui
Zhu, Jiahai
Zhu, Ya
Liu, Lixin
Zhao, Songling
Kang, Qiang
Liu, Yunxia
Zou, Hao
Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma
title Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma
title_full Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma
title_fullStr Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma
title_full_unstemmed Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma
title_short Identification of characteristic genes and construction of regulatory network in gallbladder carcinoma
title_sort identification of characteristic genes and construction of regulatory network in gallbladder carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10566037/
https://www.ncbi.nlm.nih.gov/pubmed/37821907
http://dx.doi.org/10.1186/s12920-023-01663-z
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