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Extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis

Accumulating evidence has suggested that extracellular vesicles (EVs) play a crucial role in lung cancer treatment. Thus, we aimed to investigate the modulatory role of bone marrow mesenchymal stem cell (BMSC)‐EV‐derived let‐7i and their molecular mechanism in lung cancer progression. Microarray‐bas...

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Autores principales: Liu, Jiefeng, Feng, Yuhua, Zeng, Xinyu, He, Miao, Gong, Yujing, Liu, Yiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882949/
https://www.ncbi.nlm.nih.gov/pubmed/33350586
http://dx.doi.org/10.1111/jcmm.15866
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author Liu, Jiefeng
Feng, Yuhua
Zeng, Xinyu
He, Miao
Gong, Yujing
Liu, Yiping
author_facet Liu, Jiefeng
Feng, Yuhua
Zeng, Xinyu
He, Miao
Gong, Yujing
Liu, Yiping
author_sort Liu, Jiefeng
collection PubMed
description Accumulating evidence has suggested that extracellular vesicles (EVs) play a crucial role in lung cancer treatment. Thus, we aimed to investigate the modulatory role of bone marrow mesenchymal stem cell (BMSC)‐EV‐derived let‐7i and their molecular mechanism in lung cancer progression. Microarray‐based analysis was applied to predict lung cancer‐related miRNAs and their downstream genes. RT‐qPCR and Western blot analyses were conducted to determine Let‐7i, lysine demethylase 3A (KDM3A), doublecortin‐like kinase 1 (DCLK1) and FXYD domain‐containing ion transport regulator 3 (FXYD3) expressions, after which dual‐luciferase reporter gene assay and ChIP assay were used to identify the relationship among them. After loss‐ and gain‐of‐function assays, the effects of let‐7i, KDM3A, DCLK1 and FXYD3 on the biological characteristics of lung cancer cells were assessed. Finally, tumour growth in nude mice was assessed by xenograft tumours in nude mice. Bioinformatics analysis screened out the let‐7i and its downstream gene, that is KDM3A. The findings showed the presence of a high expression of KDM3A and DCLK1 and reduced expression of let‐7i and FXYD3 in lung cancer. KDM3A elevated DCLK1 by removing the methylation of H3K9me2. Moreover, DCLK1 suppressed the FXYD3 expression. BMSC‐EV‐derived let‐7i resulted in the down‐regulation of KDM3A expression and reversed its promoting role in lung cancer development. Consistently, in vivo experiments in nude mice also confirmed that tumour growth was suppressed by the BMSC‐EV‐derived let‐7i. In conclusion, our findings demonstrated that the BMSC‐EV‐derived let‐7i possesses an inhibitory role in lung cancer progression through the KDM3A/DCLK1/FXYD3 axis, suggesting a new molecular target for lung cancer treatment.
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spelling pubmed-78829492021-02-19 Extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis Liu, Jiefeng Feng, Yuhua Zeng, Xinyu He, Miao Gong, Yujing Liu, Yiping J Cell Mol Med Original Articles Accumulating evidence has suggested that extracellular vesicles (EVs) play a crucial role in lung cancer treatment. Thus, we aimed to investigate the modulatory role of bone marrow mesenchymal stem cell (BMSC)‐EV‐derived let‐7i and their molecular mechanism in lung cancer progression. Microarray‐based analysis was applied to predict lung cancer‐related miRNAs and their downstream genes. RT‐qPCR and Western blot analyses were conducted to determine Let‐7i, lysine demethylase 3A (KDM3A), doublecortin‐like kinase 1 (DCLK1) and FXYD domain‐containing ion transport regulator 3 (FXYD3) expressions, after which dual‐luciferase reporter gene assay and ChIP assay were used to identify the relationship among them. After loss‐ and gain‐of‐function assays, the effects of let‐7i, KDM3A, DCLK1 and FXYD3 on the biological characteristics of lung cancer cells were assessed. Finally, tumour growth in nude mice was assessed by xenograft tumours in nude mice. Bioinformatics analysis screened out the let‐7i and its downstream gene, that is KDM3A. The findings showed the presence of a high expression of KDM3A and DCLK1 and reduced expression of let‐7i and FXYD3 in lung cancer. KDM3A elevated DCLK1 by removing the methylation of H3K9me2. Moreover, DCLK1 suppressed the FXYD3 expression. BMSC‐EV‐derived let‐7i resulted in the down‐regulation of KDM3A expression and reversed its promoting role in lung cancer development. Consistently, in vivo experiments in nude mice also confirmed that tumour growth was suppressed by the BMSC‐EV‐derived let‐7i. In conclusion, our findings demonstrated that the BMSC‐EV‐derived let‐7i possesses an inhibitory role in lung cancer progression through the KDM3A/DCLK1/FXYD3 axis, suggesting a new molecular target for lung cancer treatment. John Wiley and Sons Inc. 2020-12-22 2021-02 /pmc/articles/PMC7882949/ /pubmed/33350586 http://dx.doi.org/10.1111/jcmm.15866 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Jiefeng
Feng, Yuhua
Zeng, Xinyu
He, Miao
Gong, Yujing
Liu, Yiping
Extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis
title Extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis
title_full Extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis
title_fullStr Extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis
title_full_unstemmed Extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis
title_short Extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis
title_sort extracellular vesicles‐encapsulated let‐7i shed from bone mesenchymal stem cells suppress lung cancer via kdm3a/dclk1/fxyd3 axis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882949/
https://www.ncbi.nlm.nih.gov/pubmed/33350586
http://dx.doi.org/10.1111/jcmm.15866
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