The Endoplasmic Reticulum-Stressed Head and Neck Squamous Cell Carcinoma Cells Induced Exosomal miR-424-5p Inhibits Angiogenesis and Migration of Humanumbilical Vein Endothelial Cells Through LAMC1-Mediated Wnt/β-Catenin Signaling Pathway
Under endoplasmic reticulum (ER) stress, tumor plays multifaceted roles in endothelial cell dysfunction through secreting exosomal miRNAs. However, for the head and neck squamous cell carcinoma (HNSCC), it is still unclear about the impact of ER-stressed HNSCC cell derived exosomes on vascular endot...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-03-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897221083549 |
| _version_ | 1818775299517579264 |
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| author | Zeyu Wang Pengfei Jiao Yi Zhong Huan Ji Yaqin Zhang Haiyang Song Hongming Du Xu Ding Heming Wu |
| author_facet | Zeyu Wang Pengfei Jiao Yi Zhong Huan Ji Yaqin Zhang Haiyang Song Hongming Du Xu Ding Heming Wu |
| author_sort | Zeyu Wang |
| collection | DOAJ |
| description | Under endoplasmic reticulum (ER) stress, tumor plays multifaceted roles in endothelial cell dysfunction through secreting exosomal miRNAs. However, for the head and neck squamous cell carcinoma (HNSCC), it is still unclear about the impact of ER-stressed HNSCC cell derived exosomes on vascular endothelial cells. To address this gap, herein, systemic research was conducted including isolation and characterization of ER-stressed HNSCC cell (HN4 cell line as an in vitro model) derived exosomes, identification of regulatory exosomal miRNAs, target exploration and downstream signaling pathway investigation of exosomal miRNAs in human umbilical vein endothelial cell (HUVEC). ER-stressed HN4 cell-derived exosomes inhibited angiogenesis and migration of HUVEC cells in vitro . Furthermore, RNA-seq analysis demonstrated that miR-424-5p was highly upregulated in ER-stressed HN4 cell-derived exosomes. Through matrigel tube formation and transwell assays of HUVEC cells, miR-424-5p displayed great capabilities on inhibiting angiogenesis and migration. Finally, based on western blot and luciferase reporter, it was demonstrated that LAMC1 is the target of miR-424-5p which could inhibit the angiogenesis and migration of HUVEC cells by repressing the LAMC1-mediated Wnt/β-catenin signaling pathway. ER-stressed HNSCC cell-induced exosomal miR-424-5p inhibits angiogenesis and migration of HUVEC cells through LAMC1-mediated Wnt/β-catenin signaling pathway. This study offers a new insight for understanding the complicated mechanism behind ER-stress induced anti-angiogenesis of HNSCC. |
| first_indexed | 2024-12-18T10:54:50Z |
| format | Article |
| id | doaj.art-b2e4496f2b2840e0b6f0f7f693f05797 |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-12-18T10:54:50Z |
| publishDate | 2022-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-b2e4496f2b2840e0b6f0f7f693f057972022-12-21T21:10:21ZengSAGE PublishingCell Transplantation1555-38922022-03-013110.1177/09636897221083549The Endoplasmic Reticulum-Stressed Head and Neck Squamous Cell Carcinoma Cells Induced Exosomal miR-424-5p Inhibits Angiogenesis and Migration of Humanumbilical Vein Endothelial Cells Through LAMC1-Mediated Wnt/β-Catenin Signaling PathwayZeyu Wang0Pengfei Jiao1Yi Zhong2Huan Ji3Yaqin Zhang4Haiyang Song5Hongming Du6Xu Ding7Heming Wu8Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, ChinaJiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, ChinaDepartment of General Dentistry, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, ChinaJiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, ChinaKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, ChinaDepartment of General Dentistry, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, ChinaUnder endoplasmic reticulum (ER) stress, tumor plays multifaceted roles in endothelial cell dysfunction through secreting exosomal miRNAs. However, for the head and neck squamous cell carcinoma (HNSCC), it is still unclear about the impact of ER-stressed HNSCC cell derived exosomes on vascular endothelial cells. To address this gap, herein, systemic research was conducted including isolation and characterization of ER-stressed HNSCC cell (HN4 cell line as an in vitro model) derived exosomes, identification of regulatory exosomal miRNAs, target exploration and downstream signaling pathway investigation of exosomal miRNAs in human umbilical vein endothelial cell (HUVEC). ER-stressed HN4 cell-derived exosomes inhibited angiogenesis and migration of HUVEC cells in vitro . Furthermore, RNA-seq analysis demonstrated that miR-424-5p was highly upregulated in ER-stressed HN4 cell-derived exosomes. Through matrigel tube formation and transwell assays of HUVEC cells, miR-424-5p displayed great capabilities on inhibiting angiogenesis and migration. Finally, based on western blot and luciferase reporter, it was demonstrated that LAMC1 is the target of miR-424-5p which could inhibit the angiogenesis and migration of HUVEC cells by repressing the LAMC1-mediated Wnt/β-catenin signaling pathway. ER-stressed HNSCC cell-induced exosomal miR-424-5p inhibits angiogenesis and migration of HUVEC cells through LAMC1-mediated Wnt/β-catenin signaling pathway. This study offers a new insight for understanding the complicated mechanism behind ER-stress induced anti-angiogenesis of HNSCC.https://doi.org/10.1177/09636897221083549 |
| spellingShingle | Zeyu Wang Pengfei Jiao Yi Zhong Huan Ji Yaqin Zhang Haiyang Song Hongming Du Xu Ding Heming Wu The Endoplasmic Reticulum-Stressed Head and Neck Squamous Cell Carcinoma Cells Induced Exosomal miR-424-5p Inhibits Angiogenesis and Migration of Humanumbilical Vein Endothelial Cells Through LAMC1-Mediated Wnt/β-Catenin Signaling Pathway Cell Transplantation |
| title | The Endoplasmic Reticulum-Stressed Head and Neck Squamous Cell Carcinoma Cells Induced Exosomal miR-424-5p Inhibits Angiogenesis and Migration of Humanumbilical Vein Endothelial Cells Through LAMC1-Mediated Wnt/β-Catenin Signaling Pathway |
| title_full | The Endoplasmic Reticulum-Stressed Head and Neck Squamous Cell Carcinoma Cells Induced Exosomal miR-424-5p Inhibits Angiogenesis and Migration of Humanumbilical Vein Endothelial Cells Through LAMC1-Mediated Wnt/β-Catenin Signaling Pathway |
| title_fullStr | The Endoplasmic Reticulum-Stressed Head and Neck Squamous Cell Carcinoma Cells Induced Exosomal miR-424-5p Inhibits Angiogenesis and Migration of Humanumbilical Vein Endothelial Cells Through LAMC1-Mediated Wnt/β-Catenin Signaling Pathway |
| title_full_unstemmed | The Endoplasmic Reticulum-Stressed Head and Neck Squamous Cell Carcinoma Cells Induced Exosomal miR-424-5p Inhibits Angiogenesis and Migration of Humanumbilical Vein Endothelial Cells Through LAMC1-Mediated Wnt/β-Catenin Signaling Pathway |
| title_short | The Endoplasmic Reticulum-Stressed Head and Neck Squamous Cell Carcinoma Cells Induced Exosomal miR-424-5p Inhibits Angiogenesis and Migration of Humanumbilical Vein Endothelial Cells Through LAMC1-Mediated Wnt/β-Catenin Signaling Pathway |
| title_sort | endoplasmic reticulum stressed head and neck squamous cell carcinoma cells induced exosomal mir 424 5p inhibits angiogenesis and migration of humanumbilical vein endothelial cells through lamc1 mediated wnt β catenin signaling pathway |
| url | https://doi.org/10.1177/09636897221083549 |
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