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Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma

Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional rol...

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Autores principales: Morita, Takuya, Fujiwara, Tomohiro, Yoshida, Aki, Uotani, Koji, Kiyono, Masahiro, Yokoo, Suguru, Hasei, Joe, Kunisada, Toshiyuki, Ozaki, Toshifumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287053/
https://www.ncbi.nlm.nih.gov/pubmed/32523124
http://dx.doi.org/10.1038/s41598-020-66120-8
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author Morita, Takuya
Fujiwara, Tomohiro
Yoshida, Aki
Uotani, Koji
Kiyono, Masahiro
Yokoo, Suguru
Hasei, Joe
Kunisada, Toshiyuki
Ozaki, Toshifumi
author_facet Morita, Takuya
Fujiwara, Tomohiro
Yoshida, Aki
Uotani, Koji
Kiyono, Masahiro
Yokoo, Suguru
Hasei, Joe
Kunisada, Toshiyuki
Ozaki, Toshifumi
author_sort Morita, Takuya
collection PubMed
description Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.
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spelling pubmed-72870532020-06-15 Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma Morita, Takuya Fujiwara, Tomohiro Yoshida, Aki Uotani, Koji Kiyono, Masahiro Yokoo, Suguru Hasei, Joe Kunisada, Toshiyuki Ozaki, Toshifumi Sci Rep Article Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment. Nature Publishing Group UK 2020-06-10 /pmc/articles/PMC7287053/ /pubmed/32523124 http://dx.doi.org/10.1038/s41598-020-66120-8 Text en © The Author(s) 2020 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/.
spellingShingle Article
Morita, Takuya
Fujiwara, Tomohiro
Yoshida, Aki
Uotani, Koji
Kiyono, Masahiro
Yokoo, Suguru
Hasei, Joe
Kunisada, Toshiyuki
Ozaki, Toshifumi
Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma
title Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma
title_full Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma
title_fullStr Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma
title_full_unstemmed Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma
title_short Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma
title_sort clinical relevance and functional significance of cell-free microrna-1260b expression profiles in infiltrative myxofibrosarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287053/
https://www.ncbi.nlm.nih.gov/pubmed/32523124
http://dx.doi.org/10.1038/s41598-020-66120-8
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