miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells

Background. Extracellular vesicles (EVs) can deliver miRNAs between cells and play a crucial role in hepatoblastoma progression. In this study, we explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Method...

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Autores principales:	Yu Hu, Hongyan Zai, Wei Jiang, Yuanbing Yao, Zhenglin Ou, Qin Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/c726f01ecbc5458a8b2d70cd94332c4f
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spelling	oai:doaj.org-article:c726f01ecbc5458a8b2d70cd94332c4f2021-11-08T02:37:11ZmiR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells2314-715610.1155/2021/6744715https://doaj.org/article/c726f01ecbc5458a8b2d70cd94332c4f2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/6744715https://doaj.org/toc/2314-7156Background. Extracellular vesicles (EVs) can deliver miRNAs between cells and play a crucial role in hepatoblastoma progression. In this study, we explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Methods. Bioinformatics analysis was performed to explore the differentially expressed miRNAs between the hepatoblastoma and adjacent normal tissues. TEM, NTA, and western blotting were conducted to identify EVs. The expression of miR-126-3p, miR-126-5p, miR-30b-3p, miR-30b-3p, SRY, IL-1α, IL-6, and TGF-β was detected by RT-qPCR. Immunofluorescence (IF) was used to analyze the expression of PKH67, and flow cytometry was applied to assess the ratio of CD44+ CD90+ CD133+ cells. ELISA was used to evaluate the levels of IL-6 and TGF-β. A xenograft mouse model was constructed to detect the function of EVs with downregulated miR-126. IHC was performed to calculate β-catenin levels in tumor tissues. Results. miR-126 was upregulated in hepatoblastoma. EVs derived from hepatoblastoma cells significantly increased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, and TGF-β in bone marrow mesenchymal stem cells (BMSCs), while EVs with downregulated miR-126 reversed these phenomena. miR-126 downregulation notably attenuated hepatoblastoma tumor growth and decreased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, TGF-β, and β-catenin in tumor tissues of mice. Furthermore, EVs with downregulated miR-126 inhibited the differentiation of BMSCs into cancer stem cells. Conclusions. Exosomal miR-126 derived from hepatoblastoma cells promoted the tumorigenesis of liver cancer through inducing the differentiation of BMSCs into cancer stem cells.Yu HuHongyan ZaiWei JiangYuanbing YaoZhenglin OuQin ZhuHindawi LimitedarticleImmunologic diseases. AllergyRC581-607ENJournal of Immunology Research, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607
spellingShingle	Immunologic diseases. Allergy RC581-607 Yu Hu Hongyan Zai Wei Jiang Yuanbing Yao Zhenglin Ou Qin Zhu miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells
description	Background. Extracellular vesicles (EVs) can deliver miRNAs between cells and play a crucial role in hepatoblastoma progression. In this study, we explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Methods. Bioinformatics analysis was performed to explore the differentially expressed miRNAs between the hepatoblastoma and adjacent normal tissues. TEM, NTA, and western blotting were conducted to identify EVs. The expression of miR-126-3p, miR-126-5p, miR-30b-3p, miR-30b-3p, SRY, IL-1α, IL-6, and TGF-β was detected by RT-qPCR. Immunofluorescence (IF) was used to analyze the expression of PKH67, and flow cytometry was applied to assess the ratio of CD44+ CD90+ CD133+ cells. ELISA was used to evaluate the levels of IL-6 and TGF-β. A xenograft mouse model was constructed to detect the function of EVs with downregulated miR-126. IHC was performed to calculate β-catenin levels in tumor tissues. Results. miR-126 was upregulated in hepatoblastoma. EVs derived from hepatoblastoma cells significantly increased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, and TGF-β in bone marrow mesenchymal stem cells (BMSCs), while EVs with downregulated miR-126 reversed these phenomena. miR-126 downregulation notably attenuated hepatoblastoma tumor growth and decreased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, TGF-β, and β-catenin in tumor tissues of mice. Furthermore, EVs with downregulated miR-126 inhibited the differentiation of BMSCs into cancer stem cells. Conclusions. Exosomal miR-126 derived from hepatoblastoma cells promoted the tumorigenesis of liver cancer through inducing the differentiation of BMSCs into cancer stem cells.
format	article
author	Yu Hu Hongyan Zai Wei Jiang Yuanbing Yao Zhenglin Ou Qin Zhu
author_facet	Yu Hu Hongyan Zai Wei Jiang Yuanbing Yao Zhenglin Ou Qin Zhu
author_sort	Yu Hu
title	miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells
title_short	miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells
title_full	miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells
title_fullStr	miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells
title_full_unstemmed	miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells
title_sort	mir-126 in extracellular vesicles derived from hepatoblastoma cells promotes the tumorigenesis of hepatoblastoma through inducing the differentiation of bmscs into cancer stem cells
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/c726f01ecbc5458a8b2d70cd94332c4f
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miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells

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