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Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells

BACKGROUND: Hepatocellular carcinoma (HCC) is often characterized by poor prognosis, high invasiveness and chemotherapeutic resistance, and its migration is strongly dependent on the specific tumor microenvironment. Fibroblasts, such as cancer-associated stromal fibroblasts (CAFs), are the main supp...

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Autores principales: Liu, Xingchao, Wang, Hailian, Yang, Mei, Hou, Yifu, Chen, Yunfei, Bie, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797999/
https://www.ncbi.nlm.nih.gov/pubmed/35117617
http://dx.doi.org/10.21037/tcr.2020.02.68
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author Liu, Xingchao
Wang, Hailian
Yang, Mei
Hou, Yifu
Chen, Yunfei
Bie, Ping
author_facet Liu, Xingchao
Wang, Hailian
Yang, Mei
Hou, Yifu
Chen, Yunfei
Bie, Ping
author_sort Liu, Xingchao
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) is often characterized by poor prognosis, high invasiveness and chemotherapeutic resistance, and its migration is strongly dependent on the specific tumor microenvironment. Fibroblasts, such as cancer-associated stromal fibroblasts (CAFs), are the main supporting cells in the tumor microenvironment. Thus, an understanding of how these cells communicate is required for HCC treatment. METHODS: CAFs and paracancerous fibroblasts (PAFs) were isolated from patients’ surgical specimens, followed by exosome isolation and miRNA sequencing. The expression levels of miR-29b in different cell groups were detected by qPCR assay. Cell transfection with exogenous miRNAs was used to study whether the stromal cells could transfer miRNAs to HCC cells. Based on the preliminary results, a miR-29b mimic, inhibitor or miR-nonspecific mimic (miR-NSM) was further transfected into HepG2 and Huh7 cells prior to scratch wound healing and cell invasion experiments. Finally, the transfected cells were stained with Hoechst 33348. RESULTS: The direct transfer of miR-29b from CAFs to HCC cells through an exosome was observed in this study. DNA methyltransferase 3b (DNMT3b) expression was directly inhibited by miR-29b, while metastasis suppressor 1 (MTSS1) expression was upregulated in HCC cells. Such changes further induced growth arrest and inhibited HCC cell invasion. CONCLUSIONS: Exosomal miR-29b from CAFs can play a crucial role in the development, progression and metastasis of HCC. By functioning as a tumor suppressor that targets DNMT3b, miR-29b may serve as a potential therapeutic agent.
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spelling pubmed-87979992022-02-02 Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells Liu, Xingchao Wang, Hailian Yang, Mei Hou, Yifu Chen, Yunfei Bie, Ping Transl Cancer Res Original Article BACKGROUND: Hepatocellular carcinoma (HCC) is often characterized by poor prognosis, high invasiveness and chemotherapeutic resistance, and its migration is strongly dependent on the specific tumor microenvironment. Fibroblasts, such as cancer-associated stromal fibroblasts (CAFs), are the main supporting cells in the tumor microenvironment. Thus, an understanding of how these cells communicate is required for HCC treatment. METHODS: CAFs and paracancerous fibroblasts (PAFs) were isolated from patients’ surgical specimens, followed by exosome isolation and miRNA sequencing. The expression levels of miR-29b in different cell groups were detected by qPCR assay. Cell transfection with exogenous miRNAs was used to study whether the stromal cells could transfer miRNAs to HCC cells. Based on the preliminary results, a miR-29b mimic, inhibitor or miR-nonspecific mimic (miR-NSM) was further transfected into HepG2 and Huh7 cells prior to scratch wound healing and cell invasion experiments. Finally, the transfected cells were stained with Hoechst 33348. RESULTS: The direct transfer of miR-29b from CAFs to HCC cells through an exosome was observed in this study. DNA methyltransferase 3b (DNMT3b) expression was directly inhibited by miR-29b, while metastasis suppressor 1 (MTSS1) expression was upregulated in HCC cells. Such changes further induced growth arrest and inhibited HCC cell invasion. CONCLUSIONS: Exosomal miR-29b from CAFs can play a crucial role in the development, progression and metastasis of HCC. By functioning as a tumor suppressor that targets DNMT3b, miR-29b may serve as a potential therapeutic agent. AME Publishing Company 2020-04 /pmc/articles/PMC8797999/ /pubmed/35117617 http://dx.doi.org/10.21037/tcr.2020.02.68 Text en 2020 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Liu, Xingchao
Wang, Hailian
Yang, Mei
Hou, Yifu
Chen, Yunfei
Bie, Ping
Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells
title Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells
title_full Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells
title_fullStr Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells
title_full_unstemmed Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells
title_short Exosomal miR-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells
title_sort exosomal mir-29b from cancer-associated fibroblasts inhibits the migration and invasion of hepatocellular carcinoma cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797999/
https://www.ncbi.nlm.nih.gov/pubmed/35117617
http://dx.doi.org/10.21037/tcr.2020.02.68
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