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Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3
BACKGROUND/AIM: The current therapeutic strategies for endometrial cancer are limited and unsatisfactory. Accumulating evidence suggest that microRNAs (miRNAs) participate in tumor growth and metastasis. Mesenchymal stem cells (MSCs) derived exosomes (Exos) are considered as better miRNA delivery ve...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781017/ https://www.ncbi.nlm.nih.gov/pubmed/33408524 http://dx.doi.org/10.2147/CMAR.S283747 |
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author | Jing, Liang Hua, Xu Yuanna, Du Rukun, Zang Junjun, Mou |
author_facet | Jing, Liang Hua, Xu Yuanna, Du Rukun, Zang Junjun, Mou |
author_sort | Jing, Liang |
collection | PubMed |
description | BACKGROUND/AIM: The current therapeutic strategies for endometrial cancer are limited and unsatisfactory. Accumulating evidence suggest that microRNAs (miRNAs) participate in tumor growth and metastasis. Mesenchymal stem cells (MSCs) derived exosomes (Exos) are considered as better miRNA delivery vehicles. Here, we investigated the therapeutic effect of exosomal miR-499a-5p (miR-499) in human endometrial cancer metastasis. METHODS: Microarray analysis and RT-PCR were performed to detect the relative expression of miR-499 in endometrial cancer tissues and cell lines. MSC-derived Exos were characterized by transmission electron microscope (TEM), Western blot (WB), and nanoparticle tracking analysis (NTA). miR-499 was loading into Exos using electroporation. Cell proliferation and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the connection of miR-499 and VAV3. RESULTS: We found that the expression of miR-499 was significantly downregulated in cancer tissues compared with adjacent tissues in endometrial cancer patients. Moreover, exosomal miR-499 not only dramatically suppressed endometrial cancer cells proliferation, endothelial cells tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. In addition, we confirmed that miR-499 directly targets the 3′UTR sequence of VAV3. CONCLUSION: The novel identified exosomal miR-499 functions as a tumor suppressor in endometrial cancer though regulating VAV3, and these findings could be a valid molecular target for endometrial cancer therapy. |
format | Online Article Text |
id | pubmed-7781017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-77810172021-01-05 Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3 Jing, Liang Hua, Xu Yuanna, Du Rukun, Zang Junjun, Mou Cancer Manag Res Original Research BACKGROUND/AIM: The current therapeutic strategies for endometrial cancer are limited and unsatisfactory. Accumulating evidence suggest that microRNAs (miRNAs) participate in tumor growth and metastasis. Mesenchymal stem cells (MSCs) derived exosomes (Exos) are considered as better miRNA delivery vehicles. Here, we investigated the therapeutic effect of exosomal miR-499a-5p (miR-499) in human endometrial cancer metastasis. METHODS: Microarray analysis and RT-PCR were performed to detect the relative expression of miR-499 in endometrial cancer tissues and cell lines. MSC-derived Exos were characterized by transmission electron microscope (TEM), Western blot (WB), and nanoparticle tracking analysis (NTA). miR-499 was loading into Exos using electroporation. Cell proliferation and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the connection of miR-499 and VAV3. RESULTS: We found that the expression of miR-499 was significantly downregulated in cancer tissues compared with adjacent tissues in endometrial cancer patients. Moreover, exosomal miR-499 not only dramatically suppressed endometrial cancer cells proliferation, endothelial cells tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. In addition, we confirmed that miR-499 directly targets the 3′UTR sequence of VAV3. CONCLUSION: The novel identified exosomal miR-499 functions as a tumor suppressor in endometrial cancer though regulating VAV3, and these findings could be a valid molecular target for endometrial cancer therapy. Dove 2020-12-31 /pmc/articles/PMC7781017/ /pubmed/33408524 http://dx.doi.org/10.2147/CMAR.S283747 Text en © 2020 Jing et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Jing, Liang Hua, Xu Yuanna, Du Rukun, Zang Junjun, Mou Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3 |
title | Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3 |
title_full | Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3 |
title_fullStr | Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3 |
title_full_unstemmed | Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3 |
title_short | Exosomal miR-499a-5p Inhibits Endometrial Cancer Growth and Metastasis via Targeting VAV3 |
title_sort | exosomal mir-499a-5p inhibits endometrial cancer growth and metastasis via targeting vav3 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781017/ https://www.ncbi.nlm.nih.gov/pubmed/33408524 http://dx.doi.org/10.2147/CMAR.S283747 |
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