Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells
Abstract Background Angiogenesis provides essential nutrients and oxygen for tumor growth and has become the main mechanism of tumor invasion and metastasis. Exosomes are nanoscale membrane vesicles containing proteins, lipids, mRNA and microRNA (miRNA), which mediate intercellular communication and...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Cancer Cell International |
| Online Access: | https://doi.org/10.1186/s12935-021-02379-9 |
| _version_ | 1818352491183472640 |
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| author | Xuewu You Wenxiong Sun Ying Wang Xiaoli Liu Aihong Wang Lu Liu Sai Han Yu Sun Junhua Zhang Lingyu Guo Youzhong Zhang |
| author_facet | Xuewu You Wenxiong Sun Ying Wang Xiaoli Liu Aihong Wang Lu Liu Sai Han Yu Sun Junhua Zhang Lingyu Guo Youzhong Zhang |
| author_sort | Xuewu You |
| collection | DOAJ |
| description | Abstract Background Angiogenesis provides essential nutrients and oxygen for tumor growth and has become the main mechanism of tumor invasion and metastasis. Exosomes are nanoscale membrane vesicles containing proteins, lipids, mRNA and microRNA (miRNA), which mediate intercellular communication and play an important role in tumor progression. Accumulated evidence indicates that tumor-derived exosomal miRNAs participate in the tumor microenvironment and promote angiogenesis. Methods Bioinformatic target prediction and dual luciferase reporter assays were performed to identify the binding site between miR-663b and the 3′-UTR of vinculin (VCL). VCL overexpression lentivirus and miR-663b overexpression/inhibition lentivirus were used to create a VCL overexpression model and miR-663b overexpression/inhibition model in-vitro. Immunohistochemistry (IHC) assays and western blot assays were used to detect protein expression. Exosome-cell cocultures, wound healing assays, tube formation assays and transwell assays were used to measure the migration and tube formation ability of vascular endothelial cells [human umbilical vein endothelial cells (HUVECs)]. siRNA targeted VCL was used to knockdown VCL. Results In the present study, we found that miR-663b was elevated in cervical cancer tissue and exosomes. miR-663b could bind the 3′-UTR of VCL and inhibit its expression. VCL is downregulated in cervical cancer, and decreased VCL has a negative correlation with a high level of miR-663b. Further studies demonstrated that exosomes secreted by cervical cancer cells can deliver miR-663b to HUVECs and inhibit the expression of VCL, thereby promoting angiogenesis and tumor growth. Conclusions miR-663b derived from cancer cell exosomes acts as a driving factor for angiogenesis and a potential target of antiangiogenic therapy in cervical cancer. Our findings illustrated a new signaling pathway, including exosomes, miRNAs and target genes, which provides potential targets for antiangiogenic therapy. |
| first_indexed | 2024-12-13T18:54:28Z |
| format | Article |
| id | doaj.art-d0b2572e74224699ad637914111f9ab3 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-13T18:54:28Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-d0b2572e74224699ad637914111f9ab32022-12-21T23:34:50ZengBMCCancer Cell International1475-28672021-12-0121111310.1186/s12935-021-02379-9Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cellsXuewu You0Wenxiong Sun1Ying Wang2Xiaoli Liu3Aihong Wang4Lu Liu5Sai Han6Yu Sun7Junhua Zhang8Lingyu Guo9Youzhong Zhang10Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics and Gynecology, Yidu Central Hospital of WeifangDepartment of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics and Gynecology, Feicheng Hospital Affiliated to Shandong First Medical UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityAbstract Background Angiogenesis provides essential nutrients and oxygen for tumor growth and has become the main mechanism of tumor invasion and metastasis. Exosomes are nanoscale membrane vesicles containing proteins, lipids, mRNA and microRNA (miRNA), which mediate intercellular communication and play an important role in tumor progression. Accumulated evidence indicates that tumor-derived exosomal miRNAs participate in the tumor microenvironment and promote angiogenesis. Methods Bioinformatic target prediction and dual luciferase reporter assays were performed to identify the binding site between miR-663b and the 3′-UTR of vinculin (VCL). VCL overexpression lentivirus and miR-663b overexpression/inhibition lentivirus were used to create a VCL overexpression model and miR-663b overexpression/inhibition model in-vitro. Immunohistochemistry (IHC) assays and western blot assays were used to detect protein expression. Exosome-cell cocultures, wound healing assays, tube formation assays and transwell assays were used to measure the migration and tube formation ability of vascular endothelial cells [human umbilical vein endothelial cells (HUVECs)]. siRNA targeted VCL was used to knockdown VCL. Results In the present study, we found that miR-663b was elevated in cervical cancer tissue and exosomes. miR-663b could bind the 3′-UTR of VCL and inhibit its expression. VCL is downregulated in cervical cancer, and decreased VCL has a negative correlation with a high level of miR-663b. Further studies demonstrated that exosomes secreted by cervical cancer cells can deliver miR-663b to HUVECs and inhibit the expression of VCL, thereby promoting angiogenesis and tumor growth. Conclusions miR-663b derived from cancer cell exosomes acts as a driving factor for angiogenesis and a potential target of antiangiogenic therapy in cervical cancer. Our findings illustrated a new signaling pathway, including exosomes, miRNAs and target genes, which provides potential targets for antiangiogenic therapy.https://doi.org/10.1186/s12935-021-02379-9 |
| spellingShingle | Xuewu You Wenxiong Sun Ying Wang Xiaoli Liu Aihong Wang Lu Liu Sai Han Yu Sun Junhua Zhang Lingyu Guo Youzhong Zhang Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells Cancer Cell International |
| title | Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells |
| title_full | Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells |
| title_fullStr | Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells |
| title_full_unstemmed | Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells |
| title_short | Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells |
| title_sort | cervical cancer derived exosomal mir 663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells |
| url | https://doi.org/10.1186/s12935-021-02379-9 |
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