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...
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| Format: | Article |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.821650/full |
| _version_ | 1819294575279210496 |
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| author | Lin Zheng Xinyang Yue Minhui Li Jie Hu Bojin Zhang Ruijing Zhang Guoping Zheng Ruihan Chen Honglin Dong |
| author_facet | Lin Zheng Xinyang Yue Minhui Li Jie Hu Bojin Zhang Ruijing Zhang Guoping Zheng Ruihan Chen Honglin Dong |
| author_sort | Lin Zheng |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-24T04:28:30Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-24T04:28:30Z |
| publishDate | 2022-03-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-2051ba06f35f40558f7f7b5b2c96f0b82022-12-21T17:15:29ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-03-011310.3389/fgene.2022.821650821650Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and ValidationLin Zheng0Xinyang Yue1Minhui Li2Jie Hu3Bojin Zhang4Ruijing Zhang5Guoping Zheng6Ruihan Chen7Honglin Dong8Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaThe Second Hospital of Shanxi Medical University, Taiyuan, ChinaShanxi Medical University, Taiyuan, ChinaDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaFBLN5, 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.821650/fullcarotid artery diseasesgene expression profilingmicroarray analysisbiomarkerbioinformatics |
| spellingShingle | Lin Zheng Xinyang Yue Minhui Li Jie Hu Bojin Zhang Ruijing Zhang Guoping Zheng Ruihan Chen Honglin Dong Contribution of FBLN5 to Unstable Plaques in Carotid Atherosclerosis via mir128 and mir532–3p Based on Bioinformatics Prediction and Validation Frontiers in Genetics carotid artery diseases gene expression profiling microarray analysis biomarker bioinformatics |
| 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 | carotid artery diseases gene expression profiling microarray analysis biomarker bioinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.821650/full |
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