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Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway
Background: Chemotherapy resistance is a significant cause for poor prognosis of epithelial ovarian cancer (EOC). However, the molecular mechanism of chemo-resistance remains unclear, and developing available therapies and effective biomarkers for resistant EOC is in urgent demand. Stemness of cance...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10321283/ https://www.ncbi.nlm.nih.gov/pubmed/37416779 http://dx.doi.org/10.7150/ijbs.83264 |
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author | Zou, Yazhu Zhao, Zitong Wang, Jingjing Ma, Liying Liu, Yi Sun, Li Song, Yongmei |
author_facet | Zou, Yazhu Zhao, Zitong Wang, Jingjing Ma, Liying Liu, Yi Sun, Li Song, Yongmei |
author_sort | Zou, Yazhu |
collection | PubMed |
description | Background: Chemotherapy resistance is a significant cause for poor prognosis of epithelial ovarian cancer (EOC). However, the molecular mechanism of chemo-resistance remains unclear, and developing available therapies and effective biomarkers for resistant EOC is in urgent demand. Stemness of cancer cells directly results in chemo-resistance. Exosomal miRNAs rebuild tumor microenvironment (TME) and act as widely used clinical liquid biopsy markers. Methods: In our study, high throughput screenings and comprehensive analysis were performed to screen for miRNAs, which were both up-regulated in resistant EOC tissues and related to stemness, and miR-6836 was identified accordingly. Results: Clinically, high miR-6836 expression was closely correlated with poor chemotherapy response and survival for EOC patients. Functionally, miR-6836 promoted EOC cell cisplatin resistance by increasing stemness and suppressing apoptosis. Mechanistically, miR-6836 directly targeted DLG2 to enhance Yap1 nuclear translocation, and was regulated by TEAD1 forming the positive feedback loop: miR-6836-DLG2-Yap1-TEAD1. Furthermore, miR-6836 could be packaged into secreted exosomes in cisplatin-resistant EOC cells and exosomal miR-6836 was able to be delivered into cisplatin-sensitive EOC cells and reverse their cisplatin response. Conclusion: Our study revealed the molecular mechanisms of chemotherapy resistance, and identified miR-6836 as the possible therapeutic target and effective biopsy marker for resistant EOC. |
format | Online Article Text |
id | pubmed-10321283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-103212832023-07-06 Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway Zou, Yazhu Zhao, Zitong Wang, Jingjing Ma, Liying Liu, Yi Sun, Li Song, Yongmei Int J Biol Sci Research Paper Background: Chemotherapy resistance is a significant cause for poor prognosis of epithelial ovarian cancer (EOC). However, the molecular mechanism of chemo-resistance remains unclear, and developing available therapies and effective biomarkers for resistant EOC is in urgent demand. Stemness of cancer cells directly results in chemo-resistance. Exosomal miRNAs rebuild tumor microenvironment (TME) and act as widely used clinical liquid biopsy markers. Methods: In our study, high throughput screenings and comprehensive analysis were performed to screen for miRNAs, which were both up-regulated in resistant EOC tissues and related to stemness, and miR-6836 was identified accordingly. Results: Clinically, high miR-6836 expression was closely correlated with poor chemotherapy response and survival for EOC patients. Functionally, miR-6836 promoted EOC cell cisplatin resistance by increasing stemness and suppressing apoptosis. Mechanistically, miR-6836 directly targeted DLG2 to enhance Yap1 nuclear translocation, and was regulated by TEAD1 forming the positive feedback loop: miR-6836-DLG2-Yap1-TEAD1. Furthermore, miR-6836 could be packaged into secreted exosomes in cisplatin-resistant EOC cells and exosomal miR-6836 was able to be delivered into cisplatin-sensitive EOC cells and reverse their cisplatin response. Conclusion: Our study revealed the molecular mechanisms of chemotherapy resistance, and identified miR-6836 as the possible therapeutic target and effective biopsy marker for resistant EOC. Ivyspring International Publisher 2023-06-12 /pmc/articles/PMC10321283/ /pubmed/37416779 http://dx.doi.org/10.7150/ijbs.83264 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Zou, Yazhu Zhao, Zitong Wang, Jingjing Ma, Liying Liu, Yi Sun, Li Song, Yongmei Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway |
title | Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway |
title_full | Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway |
title_fullStr | Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway |
title_full_unstemmed | Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway |
title_short | Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway |
title_sort | extracellular vesicles carrying mir-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via dlg2-yap1 signaling pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10321283/ https://www.ncbi.nlm.nih.gov/pubmed/37416779 http://dx.doi.org/10.7150/ijbs.83264 |
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