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Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells
BACKGROUND: Chromobox protein homolog 7 (CBX7), a member of the Polycomb repressor complex, is a potent epigenetic regulator and gene silencer. Our group has previously reported that CBX7 functions as a tumor suppressor in ovarian cancer cells and its loss accelerated formation of carcinomatosis and...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688490/ https://www.ncbi.nlm.nih.gov/pubmed/38037081 http://dx.doi.org/10.1186/s13048-023-01312-0 |
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author | Zhang, Yi Tedja, Roslyn Millman, Michael Wong, Terrence Fox, Alexandra Chehade, Hussein Gershater, Meyer Adzibolosu, Nicholas Gogoi, Radhika Anderson, Matthew Rutherford, Thomas Zhang, Zhenggang Chopp, Michael Mor, Gil Alvero, Ayesha B. |
author_facet | Zhang, Yi Tedja, Roslyn Millman, Michael Wong, Terrence Fox, Alexandra Chehade, Hussein Gershater, Meyer Adzibolosu, Nicholas Gogoi, Radhika Anderson, Matthew Rutherford, Thomas Zhang, Zhenggang Chopp, Michael Mor, Gil Alvero, Ayesha B. |
author_sort | Zhang, Yi |
collection | PubMed |
description | BACKGROUND: Chromobox protein homolog 7 (CBX7), a member of the Polycomb repressor complex, is a potent epigenetic regulator and gene silencer. Our group has previously reported that CBX7 functions as a tumor suppressor in ovarian cancer cells and its loss accelerated formation of carcinomatosis and drove tumor progression in an ovarian cancer mouse model. The goal of this study is to identify specific signaling pathways in the ovarian tumor microenvironment that down-regulate CBX7. Given that adipocytes are an integral component of the peritoneal cavity and the ovarian tumor microenvironment, we hypothesize that the adipose microenvironment is an important regulator of CBX7 expression. RESULTS: Using conditioned media from human omental explants, we found that adipose-derived exosomes mediate CBX7 downregulation and enhance migratory potential of human ovarian cancer cells. Further, we identified adipose-derived exosomal miR-421 as a novel regulator of CBX7 expression and the main effector that downregulates CBX7. CONCLUSION: In this study, we identified miR-421 as a specific signaling pathway in the ovarian tumor microenvironment that can downregulate CBX7 to induce epigenetic change in OC cells, which can drive disease progression. These findings suggest that targeting exosomal miR-421 may curtail ovarian cancer progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01312-0. |
format | Online Article Text |
id | pubmed-10688490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106884902023-11-30 Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells Zhang, Yi Tedja, Roslyn Millman, Michael Wong, Terrence Fox, Alexandra Chehade, Hussein Gershater, Meyer Adzibolosu, Nicholas Gogoi, Radhika Anderson, Matthew Rutherford, Thomas Zhang, Zhenggang Chopp, Michael Mor, Gil Alvero, Ayesha B. J Ovarian Res Research BACKGROUND: Chromobox protein homolog 7 (CBX7), a member of the Polycomb repressor complex, is a potent epigenetic regulator and gene silencer. Our group has previously reported that CBX7 functions as a tumor suppressor in ovarian cancer cells and its loss accelerated formation of carcinomatosis and drove tumor progression in an ovarian cancer mouse model. The goal of this study is to identify specific signaling pathways in the ovarian tumor microenvironment that down-regulate CBX7. Given that adipocytes are an integral component of the peritoneal cavity and the ovarian tumor microenvironment, we hypothesize that the adipose microenvironment is an important regulator of CBX7 expression. RESULTS: Using conditioned media from human omental explants, we found that adipose-derived exosomes mediate CBX7 downregulation and enhance migratory potential of human ovarian cancer cells. Further, we identified adipose-derived exosomal miR-421 as a novel regulator of CBX7 expression and the main effector that downregulates CBX7. CONCLUSION: In this study, we identified miR-421 as a specific signaling pathway in the ovarian tumor microenvironment that can downregulate CBX7 to induce epigenetic change in OC cells, which can drive disease progression. These findings suggest that targeting exosomal miR-421 may curtail ovarian cancer progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01312-0. BioMed Central 2023-11-30 /pmc/articles/PMC10688490/ /pubmed/38037081 http://dx.doi.org/10.1186/s13048-023-01312-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhang, Yi Tedja, Roslyn Millman, Michael Wong, Terrence Fox, Alexandra Chehade, Hussein Gershater, Meyer Adzibolosu, Nicholas Gogoi, Radhika Anderson, Matthew Rutherford, Thomas Zhang, Zhenggang Chopp, Michael Mor, Gil Alvero, Ayesha B. Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells |
title | Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells |
title_full | Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells |
title_fullStr | Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells |
title_full_unstemmed | Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells |
title_short | Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells |
title_sort | adipose-derived exosomal mir-421 targets cbx7 and promotes metastatic potential in ovarian cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688490/ https://www.ncbi.nlm.nih.gov/pubmed/38037081 http://dx.doi.org/10.1186/s13048-023-01312-0 |
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