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Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation
FBLN5, a member of the short fibulins in the fibulin family of extracellular matrix/matricellular proteins, is involved in interactions with components of the basement membrane and extracellular matrix proteins. It plays key roles in endothelial tissues in many vascular diseases. In this study, the...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959633/ https://www.ncbi.nlm.nih.gov/pubmed/35356421 http://dx.doi.org/10.3389/fgene.2022.821650 |
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author | Zheng, Lin Yue, Xinyang Li, Minhui Hu, Jie Zhang, Bojin Zhang, Ruijing Zheng, Guoping Chen, Ruihan Dong, Honglin |
author_facet | Zheng, Lin Yue, Xinyang Li, Minhui Hu, Jie Zhang, Bojin Zhang, Ruijing Zheng, Guoping Chen, Ruihan Dong, Honglin |
author_sort | Zheng, Lin |
collection | PubMed |
description | FBLN5, a member of the short fibulins in the fibulin family of extracellular matrix/matricellular proteins, is involved in interactions with components of the basement membrane and extracellular matrix proteins. It plays key roles in endothelial tissues in many vascular diseases. In this study, the relationship between FBLN5 and carotid atherosclerotic plaque stability as well as the regulatory roles of miRNAs were evaluated. Differential gene expression analyses and weighted gene co-expression network analysis (WGCNA) based on the GSE163154 dataset (including 16 samples without intraplaque hemorrhage and 27 samples with intraplaque hemorrhage) in GEO revealed that FBLN5 is related to plaque stability and is the most significantly differentially expressed gene. LASSO regression was used to evaluate genes obtained from the intersection of differentially expressed genes and clinically significant modules identified by WGCNA. A prediction model based on eight genes, including FBLN5, was constructed and showed an accuracy of 0.951 based on an ROC analysis. Low FBLN5 expression in plaque tissues was confirmed by immunohistochemistry and western blotting. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that FBLN5 acted mainly by the maintenance of the cellular matrix and reactive oxygen species production. miRNAs upstream of these eight predictive genes, including FBLN5, were identified and used to construct a network diagram. These results revealed that hsa-mir-128 and hsa-mir-532–3p were upstream regulatory factors of FBLN5, as verified by PCR assays of human plaque tissues demonstrating that both miRNAs were significantly up-regulated. Therefore, FBLN5 may play an important role in carotid atherosclerosis via hsa-mir-128 and hsa-mir-532–3p as well as become an essential target for treatment. |
format | Online Article Text |
id | pubmed-8959633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89596332022-03-29 Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation Zheng, Lin Yue, Xinyang Li, Minhui Hu, Jie Zhang, Bojin Zhang, Ruijing Zheng, Guoping Chen, Ruihan Dong, Honglin Front Genet Genetics FBLN5, a member of the short fibulins in the fibulin family of extracellular matrix/matricellular proteins, is involved in interactions with components of the basement membrane and extracellular matrix proteins. It plays key roles in endothelial tissues in many vascular diseases. In this study, the relationship between FBLN5 and carotid atherosclerotic plaque stability as well as the regulatory roles of miRNAs were evaluated. Differential gene expression analyses and weighted gene co-expression network analysis (WGCNA) based on the GSE163154 dataset (including 16 samples without intraplaque hemorrhage and 27 samples with intraplaque hemorrhage) in GEO revealed that FBLN5 is related to plaque stability and is the most significantly differentially expressed gene. LASSO regression was used to evaluate genes obtained from the intersection of differentially expressed genes and clinically significant modules identified by WGCNA. A prediction model based on eight genes, including FBLN5, was constructed and showed an accuracy of 0.951 based on an ROC analysis. Low FBLN5 expression in plaque tissues was confirmed by immunohistochemistry and western blotting. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that FBLN5 acted mainly by the maintenance of the cellular matrix and reactive oxygen species production. miRNAs upstream of these eight predictive genes, including FBLN5, were identified and used to construct a network diagram. These results revealed that hsa-mir-128 and hsa-mir-532–3p were upstream regulatory factors of FBLN5, as verified by PCR assays of human plaque tissues demonstrating that both miRNAs were significantly up-regulated. Therefore, FBLN5 may play an important role in carotid atherosclerosis via hsa-mir-128 and hsa-mir-532–3p as well as become an essential target for treatment. Frontiers Media S.A. 2022-03-09 /pmc/articles/PMC8959633/ /pubmed/35356421 http://dx.doi.org/10.3389/fgene.2022.821650 Text en Copyright © 2022 Zheng, Yue, Li, Hu, Zhang, Zhang, Zheng, Chen, Dong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Zheng, Lin Yue, Xinyang Li, Minhui Hu, Jie Zhang, Bojin Zhang, Ruijing Zheng, Guoping Chen, Ruihan Dong, Honglin Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation |
title | Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation |
title_full | Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation |
title_fullStr | Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation |
title_full_unstemmed | Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation |
title_short | Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation |
title_sort | contribution of fbln5 to unstable plaques in carotid atherosclerosis via mir128 and mir532–3p based on bioinformatics prediction and validation |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959633/ https://www.ncbi.nlm.nih.gov/pubmed/35356421 http://dx.doi.org/10.3389/fgene.2022.821650 |
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