Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential Stress
Background. Numerous studies have highlighted that long noncoding RNA (lncRNA) can indirectly regulate the expression of mRNAs by binding to microRNA (miRNA). LncRNA-associated ceRNA networks play a vital role in the initiation and progression of several pathological mechanisms. However, the lncRNA-...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Cardiology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2020/1481937 |
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| author | Zhuhui Huang William Adiwignya Winata Kui Zhang Yang Zhao Yang Li Ning Zhou Shaoyou Zhou Wei Fu Bokang Qiao Guoqi Li Yihui Shao Jubing Zheng Ran Dong |
| author_facet | Zhuhui Huang William Adiwignya Winata Kui Zhang Yang Zhao Yang Li Ning Zhou Shaoyou Zhou Wei Fu Bokang Qiao Guoqi Li Yihui Shao Jubing Zheng Ran Dong |
| author_sort | Zhuhui Huang |
| collection | DOAJ |
| description | Background. Numerous studies have highlighted that long noncoding RNA (lncRNA) can indirectly regulate the expression of mRNAs by binding to microRNA (miRNA). LncRNA-associated ceRNA networks play a vital role in the initiation and progression of several pathological mechanisms. However, the lncRNA-miRNA-mRNA ceRNA network in endothelial cells under cyclic stretch is seldom studied. Methods. The miRNA, mRNA, and lncRNA expression profiles of 6 human umbilical vein endothelial cells (HUVECs) under circumferential stress were obtained by next-generation sequencing (NGS). We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the R software package GDCRNATools. Cytoscape was adopted to construct a lncRNA-miRNA-mRNA ceRNA network. In addition, through GO and KEGG pathway annotations, we analyzed gene functions and their related pathways. We also adopted ELISA and TUNEL to investigate the effect of si-NEAT1 on endothelial inflammation and apoptosis. Results. We recognized a total of 32978 lncRNAs, 1046 miRNAs, and 31958 mRNAs in 6 samples; among them, 155 different expressed lncRNAs, 74 different expressed miRNAs, and 960 different mRNAs were adopted. Based on the established theory, the ceRNA network was composed of 13 lncRNAs, 44 miRNAs, and 115 mRNAs. We constructed and visualized a lncRNA-miRNA-mRNA network, and the top 20 nodes are identified after calculating their degrees. The nodes with most degrees in three kinds of RNAs are hsa-miR-4739, NEAT1, and MAP3K2. Functional analysis showed that different biological processes enriched in biological regulation, response to stimulus and cell communication. Pathway analysis was mainly enriched in longevity regulating, cell cycle, mTOR, and FoxO signaling pathway. Circumferential stress can significantly downregulate NEAT1, and after transducing si-NEAT1 for 24 h, inflammatory cytokine IL-6 and MCP-1 were significantly increased; furthermore, fewer TUNEL-positive cells were found in the si-NEAT1 treated group. Conclusions. The establishing of a ceRNA network can help further understand the mechanism of vein graft failure. Our data demonstrated that NEAT1 may be a core factor among the mechanical stress factors and that cyclic stress can significantly reduce expression of NEAT1, give rise to inflammation in the early stage of endothelial dysfunction, and promote EC apoptosis, which may play an essential role in vein graft failure. |
| format | Article |
| id | doaj-art-ae3445b1a1e244dc9eb24fc01a984df0 |
| institution | Kabale University |
| issn | 2090-8016 2090-0597 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cardiology Research and Practice |
| spelling | doaj-art-ae3445b1a1e244dc9eb24fc01a984df02025-08-20T03:38:59ZengWileyCardiology Research and Practice2090-80162090-05972020-01-01202010.1155/2020/14819371481937Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential StressZhuhui Huang0William Adiwignya Winata1Kui Zhang2Yang Zhao3Yang Li4Ning Zhou5Shaoyou Zhou6Wei Fu7Bokang Qiao8Guoqi Li9Yihui Shao10Jubing Zheng11Ran Dong12Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaKey Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education and Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaKey Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education and Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaKey Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education and Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, ChinaBackground. Numerous studies have highlighted that long noncoding RNA (lncRNA) can indirectly regulate the expression of mRNAs by binding to microRNA (miRNA). LncRNA-associated ceRNA networks play a vital role in the initiation and progression of several pathological mechanisms. However, the lncRNA-miRNA-mRNA ceRNA network in endothelial cells under cyclic stretch is seldom studied. Methods. The miRNA, mRNA, and lncRNA expression profiles of 6 human umbilical vein endothelial cells (HUVECs) under circumferential stress were obtained by next-generation sequencing (NGS). We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the R software package GDCRNATools. Cytoscape was adopted to construct a lncRNA-miRNA-mRNA ceRNA network. In addition, through GO and KEGG pathway annotations, we analyzed gene functions and their related pathways. We also adopted ELISA and TUNEL to investigate the effect of si-NEAT1 on endothelial inflammation and apoptosis. Results. We recognized a total of 32978 lncRNAs, 1046 miRNAs, and 31958 mRNAs in 6 samples; among them, 155 different expressed lncRNAs, 74 different expressed miRNAs, and 960 different mRNAs were adopted. Based on the established theory, the ceRNA network was composed of 13 lncRNAs, 44 miRNAs, and 115 mRNAs. We constructed and visualized a lncRNA-miRNA-mRNA network, and the top 20 nodes are identified after calculating their degrees. The nodes with most degrees in three kinds of RNAs are hsa-miR-4739, NEAT1, and MAP3K2. Functional analysis showed that different biological processes enriched in biological regulation, response to stimulus and cell communication. Pathway analysis was mainly enriched in longevity regulating, cell cycle, mTOR, and FoxO signaling pathway. Circumferential stress can significantly downregulate NEAT1, and after transducing si-NEAT1 for 24 h, inflammatory cytokine IL-6 and MCP-1 were significantly increased; furthermore, fewer TUNEL-positive cells were found in the si-NEAT1 treated group. Conclusions. The establishing of a ceRNA network can help further understand the mechanism of vein graft failure. Our data demonstrated that NEAT1 may be a core factor among the mechanical stress factors and that cyclic stress can significantly reduce expression of NEAT1, give rise to inflammation in the early stage of endothelial dysfunction, and promote EC apoptosis, which may play an essential role in vein graft failure.http://dx.doi.org/10.1155/2020/1481937 |
| spellingShingle | Zhuhui Huang William Adiwignya Winata Kui Zhang Yang Zhao Yang Li Ning Zhou Shaoyou Zhou Wei Fu Bokang Qiao Guoqi Li Yihui Shao Jubing Zheng Ran Dong Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential Stress Cardiology Research and Practice |
| title | Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential Stress |
| title_full | Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential Stress |
| title_fullStr | Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential Stress |
| title_full_unstemmed | Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential Stress |
| title_short | Reconstruction of a lncRNA-Associated ceRNA Network in Endothelial Cells under Circumferential Stress |
| title_sort | reconstruction of a lncrna associated cerna network in endothelial cells under circumferential stress |
| url | http://dx.doi.org/10.1155/2020/1481937 |
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