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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: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659572/ https://www.ncbi.nlm.nih.gov/pubmed/37986971 http://dx.doi.org/10.1101/2023.11.07.566022 |
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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. |
format | Online Article Text |
id | pubmed-10659572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-106595722023-11-20 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. bioRxiv Article 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. Cold Spring Harbor Laboratory 2023-11-10 /pmc/articles/PMC10659572/ /pubmed/37986971 http://dx.doi.org/10.1101/2023.11.07.566022 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article 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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659572/ https://www.ncbi.nlm.nih.gov/pubmed/37986971 http://dx.doi.org/10.1101/2023.11.07.566022 |
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