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Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism
BACKGROUND: Chemoresistance poses a great hindrance in the treatment of breast cancer (BC). Interestingly, exosome (Exo)-mediated transfer of long noncoding RNAs (lncRNAs) has been reported to regulate chemoresistance in diverse diseases. We herein investigate the potential role of lncRNA metastasis...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262507/ https://www.ncbi.nlm.nih.gov/pubmed/35813865 http://dx.doi.org/10.1155/2022/5483523 |
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author | Tao, Shuang Bai, Zhengyang Liu, Yaobang Gao, Yali Zhou, Jia Zhang, Yangyang Li, Jinping |
author_facet | Tao, Shuang Bai, Zhengyang Liu, Yaobang Gao, Yali Zhou, Jia Zhang, Yangyang Li, Jinping |
author_sort | Tao, Shuang |
collection | PubMed |
description | BACKGROUND: Chemoresistance poses a great hindrance in the treatment of breast cancer (BC). Interestingly, exosome (Exo)-mediated transfer of long noncoding RNAs (lncRNAs) has been reported to regulate chemoresistance in diverse diseases. We herein investigate the potential role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) transferred by BC cell-derived Exo in chemoresistance of BC cells. METHODS: BC-related lncRNAs were identified. Exosomes were isolated and verified from BC cells. The expression patterns of MALAT1 were then examined in the adriamycin (ADR)-sensitive and resistant cells and the isolated Exo, followed by the analysis of the downstream microRNA (miRNA) of MALAT1. The role and mechanism of MALAT1 transmitted by BC cell-derived Exo in BC cell metastasis and chemoresistance were assessed. RESULTS: MALAT1 was highly expressed in BC cells and their Exo. In addition, MALAT1 delivered by BC cell-derived Exo augmented the malignant properties and chemoresistance of BC cells. Mechanistically, MALAT1 bound to miR-1-3p and limited the miR-1-3p expression, which sequentially targeted the vasodilator-stimulated phosphoprotein (VASP) protein. Moreover, silencing of VASP inhibited the activation of the RAP1 member of RAS oncogene family (Rap1) signaling pathway, which led to the attenuation of BC cell malignant properties and chemoresistance. In vivo assay further validated the tumor-promoting effect of Exo-MALAT1 via regulation of the miR-1-3p/VASP/Rap1 axis. CONCLUSION: Collectively, MALAT1 loaded by BC cell-derived Exo can accelerate BC cell metastasis and chemoresistance via disruption of miR-1-3p-mediated inhibition of the VASP/Rap1 signaling axis. |
format | Online Article Text |
id | pubmed-9262507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-92625072022-07-08 Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism Tao, Shuang Bai, Zhengyang Liu, Yaobang Gao, Yali Zhou, Jia Zhang, Yangyang Li, Jinping J Oncol Research Article BACKGROUND: Chemoresistance poses a great hindrance in the treatment of breast cancer (BC). Interestingly, exosome (Exo)-mediated transfer of long noncoding RNAs (lncRNAs) has been reported to regulate chemoresistance in diverse diseases. We herein investigate the potential role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) transferred by BC cell-derived Exo in chemoresistance of BC cells. METHODS: BC-related lncRNAs were identified. Exosomes were isolated and verified from BC cells. The expression patterns of MALAT1 were then examined in the adriamycin (ADR)-sensitive and resistant cells and the isolated Exo, followed by the analysis of the downstream microRNA (miRNA) of MALAT1. The role and mechanism of MALAT1 transmitted by BC cell-derived Exo in BC cell metastasis and chemoresistance were assessed. RESULTS: MALAT1 was highly expressed in BC cells and their Exo. In addition, MALAT1 delivered by BC cell-derived Exo augmented the malignant properties and chemoresistance of BC cells. Mechanistically, MALAT1 bound to miR-1-3p and limited the miR-1-3p expression, which sequentially targeted the vasodilator-stimulated phosphoprotein (VASP) protein. Moreover, silencing of VASP inhibited the activation of the RAP1 member of RAS oncogene family (Rap1) signaling pathway, which led to the attenuation of BC cell malignant properties and chemoresistance. In vivo assay further validated the tumor-promoting effect of Exo-MALAT1 via regulation of the miR-1-3p/VASP/Rap1 axis. CONCLUSION: Collectively, MALAT1 loaded by BC cell-derived Exo can accelerate BC cell metastasis and chemoresistance via disruption of miR-1-3p-mediated inhibition of the VASP/Rap1 signaling axis. Hindawi 2022-06-30 /pmc/articles/PMC9262507/ /pubmed/35813865 http://dx.doi.org/10.1155/2022/5483523 Text en Copyright © 2022 Shuang Tao et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Tao, Shuang Bai, Zhengyang Liu, Yaobang Gao, Yali Zhou, Jia Zhang, Yangyang Li, Jinping Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism |
title | Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism |
title_full | Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism |
title_fullStr | Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism |
title_full_unstemmed | Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism |
title_short | Exosomes Derived from Tumor Cells Initiate Breast Cancer Cell Metastasis and Chemoresistance through a MALAT1-Dependent Mechanism |
title_sort | exosomes derived from tumor cells initiate breast cancer cell metastasis and chemoresistance through a malat1-dependent mechanism |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262507/ https://www.ncbi.nlm.nih.gov/pubmed/35813865 http://dx.doi.org/10.1155/2022/5483523 |
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