Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p

The mechanisms underlying the effects of cancer-associated fibroblasts (CAFs) on cancer stemness and tumor progression in renal cell carcinoma (RCC) have not been elucidated yet. In the present study, we found that the enrichment of CAFs was positively associated with tumor progression and cancer st...

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Autores principales: Ding, Meng, Zhao, Xiaozhi, Chen, Xiaoqing, Diao, Wenli, Kan, Yansheng, Cao, Wenmin, Chen, Wei, Jiang, Bo, Qin, Haixiang, Gao, Jie, Zhuang, Junlong, Zhang, Qing, Guo, Hongqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626570/
https://www.ncbi.nlm.nih.gov/pubmed/36319622
http://dx.doi.org/10.1038/s41420-022-01219-7
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author Ding, Meng
Zhao, Xiaozhi
Chen, Xiaoqing
Diao, Wenli
Kan, Yansheng
Cao, Wenmin
Chen, Wei
Jiang, Bo
Qin, Haixiang
Gao, Jie
Zhuang, Junlong
Zhang, Qing
Guo, Hongqian
author_facet Ding, Meng
Zhao, Xiaozhi
Chen, Xiaoqing
Diao, Wenli
Kan, Yansheng
Cao, Wenmin
Chen, Wei
Jiang, Bo
Qin, Haixiang
Gao, Jie
Zhuang, Junlong
Zhang, Qing
Guo, Hongqian
author_sort Ding, Meng
collection PubMed
description The mechanisms underlying the effects of cancer-associated fibroblasts (CAFs) on cancer stemness and tumor progression in renal cell carcinoma (RCC) have not been elucidated yet. In the present study, we found that the enrichment of CAFs was positively associated with tumor progression and cancer stemness in RCC. Further investigation revealed that CAFs could enhance cancer stemness through delivering exosomes to RCC cells, and miR-181d-5p was identified as the critical exosomal miRNA in CAF-secreted exosomes by small RNA sequencing and subsequent screening assays. Mechanistically, exosomal miR-181d-5p transferred from CAFs to RCC cells directly suppressed the expression of ring finger protein 43 (RNF43) and activated Wnt/β-catenin signaling pathway, thus promoted cancer stemness and tumor progression. Overexpression of RNF43 strongly suppressed stemness properties and the effects could be reverted by miR-181d-5p. Overall, our findings revealed a crucial mechanism by which CAF-secreted exosomal miRNAs to enhance cancer stemness and thus promote RCC progression, suggesting a new avenue based on CAF-secreted miRNAs for more effective targeted therapies.
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spelling pubmed-96265702022-11-03 Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p Ding, Meng Zhao, Xiaozhi Chen, Xiaoqing Diao, Wenli Kan, Yansheng Cao, Wenmin Chen, Wei Jiang, Bo Qin, Haixiang Gao, Jie Zhuang, Junlong Zhang, Qing Guo, Hongqian Cell Death Discov Article The mechanisms underlying the effects of cancer-associated fibroblasts (CAFs) on cancer stemness and tumor progression in renal cell carcinoma (RCC) have not been elucidated yet. In the present study, we found that the enrichment of CAFs was positively associated with tumor progression and cancer stemness in RCC. Further investigation revealed that CAFs could enhance cancer stemness through delivering exosomes to RCC cells, and miR-181d-5p was identified as the critical exosomal miRNA in CAF-secreted exosomes by small RNA sequencing and subsequent screening assays. Mechanistically, exosomal miR-181d-5p transferred from CAFs to RCC cells directly suppressed the expression of ring finger protein 43 (RNF43) and activated Wnt/β-catenin signaling pathway, thus promoted cancer stemness and tumor progression. Overexpression of RNF43 strongly suppressed stemness properties and the effects could be reverted by miR-181d-5p. Overall, our findings revealed a crucial mechanism by which CAF-secreted exosomal miRNAs to enhance cancer stemness and thus promote RCC progression, suggesting a new avenue based on CAF-secreted miRNAs for more effective targeted therapies. Nature Publishing Group UK 2022-11-01 /pmc/articles/PMC9626570/ /pubmed/36319622 http://dx.doi.org/10.1038/s41420-022-01219-7 Text en © The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ding, Meng
Zhao, Xiaozhi
Chen, Xiaoqing
Diao, Wenli
Kan, Yansheng
Cao, Wenmin
Chen, Wei
Jiang, Bo
Qin, Haixiang
Gao, Jie
Zhuang, Junlong
Zhang, Qing
Guo, Hongqian
Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p
title Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p
title_full Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p
title_fullStr Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p
title_full_unstemmed Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p
title_short Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p
title_sort cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal mir-181d-5p
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626570/
https://www.ncbi.nlm.nih.gov/pubmed/36319622
http://dx.doi.org/10.1038/s41420-022-01219-7
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