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Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB
M2-like polarized tumor-associated macrophages (TAMs) are the major component of infiltrating immune cells in hepatocellular carcinoma (HCC), which have been proved to exhibit significant immunosuppressive and pro-tumoral effects. However, the underlying mechanism of the tumor microenvironment (TME)...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003272/ https://www.ncbi.nlm.nih.gov/pubmed/36902024 http://dx.doi.org/10.3390/ijms24054593 |
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author | Yu, Haiyang Pan, Jing Zheng, Siyue Cai, Deyang Luo, Aixiang Xia, Zanxian Huang, Jufang |
author_facet | Yu, Haiyang Pan, Jing Zheng, Siyue Cai, Deyang Luo, Aixiang Xia, Zanxian Huang, Jufang |
author_sort | Yu, Haiyang |
collection | PubMed |
description | M2-like polarized tumor-associated macrophages (TAMs) are the major component of infiltrating immune cells in hepatocellular carcinoma (HCC), which have been proved to exhibit significant immunosuppressive and pro-tumoral effects. However, the underlying mechanism of the tumor microenvironment (TME) educating TAMs to express M2-like phenotypes is still not fully understood. Here, we report that HCC-derived exosomes are involved in intercellular communications and exhibit a greater capacity to mediate TAMs’ phenotypic differentiation. In our study, HCC cell-derived exosomes were collected and used to treat THP-1 cells in vitro. Quantitative polymerase chain reaction (qPCR) results showed that the exosomes significantly promoted THP-1 macrophages to differentiate into M2-like macrophages, which have a high production of transforming growth factor-β (TGF-β) and interleukin (IL)-10. The analysis of bioinformatics indicated that exosomal miR-21-5p is closely related to TAM differentiation and is associated with unfavorable prognosis in HCC. Overexpressing miR-21-5p in human monocyte-derived leukemia (THP-1) cells induced down-regulation of IL-1β levels; however, it enhanced production of IL-10 and promoted the malignant growth of HCC cells in vitro. A reporter assay confirmed that miR-21-5p directly targeted Ras homolog family member B (RhoB) 3′-untranslatedregion (UTR) in THP-1 cells. Downregulated RhoB levels in THP-1 cells would weaken mitogen-activated protein kinase (MAPK) axis signaling pathways. Taken together, tumor-derived miR-21-5p promote the malignant advance of HCC, which mediated intercellular crosstalk between tumor cells and macrophages. Targeting M2-like TAMs and intercepting their associated signaling pathways would provide potentially specific and novel therapeutic approaches for HCC treatment. |
format | Online Article Text |
id | pubmed-10003272 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100032722023-03-11 Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB Yu, Haiyang Pan, Jing Zheng, Siyue Cai, Deyang Luo, Aixiang Xia, Zanxian Huang, Jufang Int J Mol Sci Article M2-like polarized tumor-associated macrophages (TAMs) are the major component of infiltrating immune cells in hepatocellular carcinoma (HCC), which have been proved to exhibit significant immunosuppressive and pro-tumoral effects. However, the underlying mechanism of the tumor microenvironment (TME) educating TAMs to express M2-like phenotypes is still not fully understood. Here, we report that HCC-derived exosomes are involved in intercellular communications and exhibit a greater capacity to mediate TAMs’ phenotypic differentiation. In our study, HCC cell-derived exosomes were collected and used to treat THP-1 cells in vitro. Quantitative polymerase chain reaction (qPCR) results showed that the exosomes significantly promoted THP-1 macrophages to differentiate into M2-like macrophages, which have a high production of transforming growth factor-β (TGF-β) and interleukin (IL)-10. The analysis of bioinformatics indicated that exosomal miR-21-5p is closely related to TAM differentiation and is associated with unfavorable prognosis in HCC. Overexpressing miR-21-5p in human monocyte-derived leukemia (THP-1) cells induced down-regulation of IL-1β levels; however, it enhanced production of IL-10 and promoted the malignant growth of HCC cells in vitro. A reporter assay confirmed that miR-21-5p directly targeted Ras homolog family member B (RhoB) 3′-untranslatedregion (UTR) in THP-1 cells. Downregulated RhoB levels in THP-1 cells would weaken mitogen-activated protein kinase (MAPK) axis signaling pathways. Taken together, tumor-derived miR-21-5p promote the malignant advance of HCC, which mediated intercellular crosstalk between tumor cells and macrophages. Targeting M2-like TAMs and intercepting their associated signaling pathways would provide potentially specific and novel therapeutic approaches for HCC treatment. MDPI 2023-02-27 /pmc/articles/PMC10003272/ /pubmed/36902024 http://dx.doi.org/10.3390/ijms24054593 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yu, Haiyang Pan, Jing Zheng, Siyue Cai, Deyang Luo, Aixiang Xia, Zanxian Huang, Jufang Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB |
title | Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB |
title_full | Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB |
title_fullStr | Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB |
title_full_unstemmed | Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB |
title_short | Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB |
title_sort | hepatocellular carcinoma cell-derived exosomal mir-21-5p induces macrophage m2 polarization by targeting rhob |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003272/ https://www.ncbi.nlm.nih.gov/pubmed/36902024 http://dx.doi.org/10.3390/ijms24054593 |
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