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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...

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Autores principales: Jing, Liang, Hua, Xu, Yuanna, Du, Rukun, Zang, Junjun, Mou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
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.
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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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