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Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer
BACKGROUND: Cancer‐associated fibroblasts (CAFs) contributes to overall tumor progression. In the current survey, we explored the ability of microRNA‐20a (miR‐20a) within these CAF‐derived exosomes to influence non‐small‐cell lung cancer (NSCLC) progression. MATERIALS AND METHODS: Normal tissue‐asso...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299573/ https://www.ncbi.nlm.nih.gov/pubmed/35857905 http://dx.doi.org/10.1002/ctm2.989 |
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author | Shi, Lin Zhu, Weiliang Huang, Yuanyuan Zhuo, Lin Wang, Siyun Chen, Shaobing Zhang, Bei Ke, Bin |
author_facet | Shi, Lin Zhu, Weiliang Huang, Yuanyuan Zhuo, Lin Wang, Siyun Chen, Shaobing Zhang, Bei Ke, Bin |
author_sort | Shi, Lin |
collection | PubMed |
description | BACKGROUND: Cancer‐associated fibroblasts (CAFs) contributes to overall tumor progression. In the current survey, we explored the ability of microRNA‐20a (miR‐20a) within these CAF‐derived exosomes to influence non‐small‐cell lung cancer (NSCLC) progression. MATERIALS AND METHODS: Normal tissue‐associated fibroblasts (NAFs) and CAFs were collected from samples of NSCLC patient tumors and paracancerous lung tissues. Exosomes derived from these cells were then characterized via Western blotting, nanoparticle tracking analyses, and transmission electron microscopy. The expression of miR‐20a was assessed via qPCR and fluorescence in situ hybridization (FISH). CCK‐8, EdU uptake, and colony formation assessments were used for evaluating tumor proliferation, while Hoechst staining was performed to monitor the in vitro apoptotic death of tumor cells. A model of xenograft tumor established in nude mice was also used to evaluate in vivo tumor responses. RESULTS: CAF‐derived exosomes exhibited miR‐20a upregulation and promoted NSCLC cell proliferation and resistance to cisplatin (DDP). Mechanistically, CAF‐derived exosomes were discovered to transmit miR‐20a to tumor cells wherein it was able to target PTEN to enhance DDP resistance and proliferation. Associated PTEN downregulation following exosome‐derived miR‐20a treatment enhanced PI3K/AKT pathway activation. CONCLUSION: The achieved outcomes explain that CAFs can release miR‐20a‐containing exosomes capable of promoting NSCLC progression and chemoresistance, highlighting this pathway as a possible therapeutic target in NSCLC. |
format | Online Article Text |
id | pubmed-9299573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92995732022-07-22 Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer Shi, Lin Zhu, Weiliang Huang, Yuanyuan Zhuo, Lin Wang, Siyun Chen, Shaobing Zhang, Bei Ke, Bin Clin Transl Med Research Articles BACKGROUND: Cancer‐associated fibroblasts (CAFs) contributes to overall tumor progression. In the current survey, we explored the ability of microRNA‐20a (miR‐20a) within these CAF‐derived exosomes to influence non‐small‐cell lung cancer (NSCLC) progression. MATERIALS AND METHODS: Normal tissue‐associated fibroblasts (NAFs) and CAFs were collected from samples of NSCLC patient tumors and paracancerous lung tissues. Exosomes derived from these cells were then characterized via Western blotting, nanoparticle tracking analyses, and transmission electron microscopy. The expression of miR‐20a was assessed via qPCR and fluorescence in situ hybridization (FISH). CCK‐8, EdU uptake, and colony formation assessments were used for evaluating tumor proliferation, while Hoechst staining was performed to monitor the in vitro apoptotic death of tumor cells. A model of xenograft tumor established in nude mice was also used to evaluate in vivo tumor responses. RESULTS: CAF‐derived exosomes exhibited miR‐20a upregulation and promoted NSCLC cell proliferation and resistance to cisplatin (DDP). Mechanistically, CAF‐derived exosomes were discovered to transmit miR‐20a to tumor cells wherein it was able to target PTEN to enhance DDP resistance and proliferation. Associated PTEN downregulation following exosome‐derived miR‐20a treatment enhanced PI3K/AKT pathway activation. CONCLUSION: The achieved outcomes explain that CAFs can release miR‐20a‐containing exosomes capable of promoting NSCLC progression and chemoresistance, highlighting this pathway as a possible therapeutic target in NSCLC. John Wiley and Sons Inc. 2022-07-20 /pmc/articles/PMC9299573/ /pubmed/35857905 http://dx.doi.org/10.1002/ctm2.989 Text en © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Shi, Lin Zhu, Weiliang Huang, Yuanyuan Zhuo, Lin Wang, Siyun Chen, Shaobing Zhang, Bei Ke, Bin Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer |
title | Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer |
title_full | Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer |
title_fullStr | Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer |
title_full_unstemmed | Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer |
title_short | Cancer‐associated fibroblast‐derived exosomal microRNA‐20a suppresses the PTEN/PI3K‐AKT pathway to promote the progression and chemoresistance of non‐small cell lung cancer |
title_sort | cancer‐associated fibroblast‐derived exosomal microrna‐20a suppresses the pten/pi3k‐akt pathway to promote the progression and chemoresistance of non‐small cell lung cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299573/ https://www.ncbi.nlm.nih.gov/pubmed/35857905 http://dx.doi.org/10.1002/ctm2.989 |
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