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miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A

BACKGROUND: Emerging proof suggests that microRNA (miRNA) malfunction is correlated to the generation and development of multiple malignancies. It has been proven that miRNA (miR)-139 represses a variety of malignancies. However, the understanding of its impact on ovarian cancer (OC) is insufficient...

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Autores principales: Xiao, Fang, Xiao, Songshu, Xue, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904246/
https://www.ncbi.nlm.nih.gov/pubmed/31839712
http://dx.doi.org/10.2147/OTT.S221236
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author Xiao, Fang
Xiao, Songshu
Xue, Min
author_facet Xiao, Fang
Xiao, Songshu
Xue, Min
author_sort Xiao, Fang
collection PubMed
description BACKGROUND: Emerging proof suggests that microRNA (miRNA) malfunction is correlated to the generation and development of multiple malignancies. It has been proven that miRNA (miR)-139 represses a variety of malignancies. However, the understanding of its impact on ovarian cancer (OC) is insufficient. We aimed to investigate the expression and function of miR-139 in OC. METHODS: The expression of mir-139 was detected and recorded, and the relationship of mir-139 remaining OC cells was explored. At the same time, we studied the correlation between ATP7A and mir-139 by the luciferase reporter test, Western blot, and quantitative real-time reverse transcription PCR. RESULTS: The expression of miR-139 was remarkably downregulated in OC specimens. Furthermore, excessive miR-139 expression noticeably inhibited the migration, colony generation, proliferation, and invasion of OC cells. In addition, excessive miR-139 expression remarkably repressed the death and the expression of proteins related to cell death in OC cells, as well as inhibited the shedding of exosomes. According to the luciferase reporter test, Western blot, and quantitative real-time reverse transcription PCR, miR-139 directly targeted ATP7A. Furthermore, the expression of ATP7A was found to be negatively related to miR-139 levels in OC specimens. It was revealed via a rescue experiment that excessive ATP7A expression counteracted the repressive effect of miR-139 in OC cells. CONCLUSION: It was revealed via an in vivo study that miR-139 remarkably inhibited the growth of malignancies by downregulating ATP7A in nude mice. miR-139 represses the development of malignancies in OC by directly targeting ATP7A, offering an innovative approach for molecular therapy of OC.
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spelling pubmed-69042462019-12-13 miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A Xiao, Fang Xiao, Songshu Xue, Min Onco Targets Ther Original Research BACKGROUND: Emerging proof suggests that microRNA (miRNA) malfunction is correlated to the generation and development of multiple malignancies. It has been proven that miRNA (miR)-139 represses a variety of malignancies. However, the understanding of its impact on ovarian cancer (OC) is insufficient. We aimed to investigate the expression and function of miR-139 in OC. METHODS: The expression of mir-139 was detected and recorded, and the relationship of mir-139 remaining OC cells was explored. At the same time, we studied the correlation between ATP7A and mir-139 by the luciferase reporter test, Western blot, and quantitative real-time reverse transcription PCR. RESULTS: The expression of miR-139 was remarkably downregulated in OC specimens. Furthermore, excessive miR-139 expression noticeably inhibited the migration, colony generation, proliferation, and invasion of OC cells. In addition, excessive miR-139 expression remarkably repressed the death and the expression of proteins related to cell death in OC cells, as well as inhibited the shedding of exosomes. According to the luciferase reporter test, Western blot, and quantitative real-time reverse transcription PCR, miR-139 directly targeted ATP7A. Furthermore, the expression of ATP7A was found to be negatively related to miR-139 levels in OC specimens. It was revealed via a rescue experiment that excessive ATP7A expression counteracted the repressive effect of miR-139 in OC cells. CONCLUSION: It was revealed via an in vivo study that miR-139 remarkably inhibited the growth of malignancies by downregulating ATP7A in nude mice. miR-139 represses the development of malignancies in OC by directly targeting ATP7A, offering an innovative approach for molecular therapy of OC. Dove 2019-12-06 /pmc/articles/PMC6904246/ /pubmed/31839712 http://dx.doi.org/10.2147/OTT.S221236 Text en © 2019 Xiao 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
Xiao, Fang
Xiao, Songshu
Xue, Min
miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A
title miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A
title_full miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A
title_fullStr miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A
title_full_unstemmed miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A
title_short miR-139 Controls Viability Of Ovarian Cancer Cells Through Apoptosis Induction And Exosome Shedding Inhibition By Targeting ATP7A
title_sort mir-139 controls viability of ovarian cancer cells through apoptosis induction and exosome shedding inhibition by targeting atp7a
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904246/
https://www.ncbi.nlm.nih.gov/pubmed/31839712
http://dx.doi.org/10.2147/OTT.S221236
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