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Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway

Objective: Esophageal squamous cell carcinoma (ESCC) presents high morbidity and mortality. It was demonstrated that blood-derived vesicles can facilitate ESCC development and transmit regulating signals. However, the molecular mechanism of vesicle miRNA secreted by tumor cells affecting ESCC progre...

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Autores principales: He, Binjun, Zhang, Kang, Han, Xiaoliang, Su, Chao, Zhao, Jiaming, Wang, Guoxia, Wang, Guzong, Zhang, Liuya, Hu, Wenbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927724/
https://www.ncbi.nlm.nih.gov/pubmed/35309127
http://dx.doi.org/10.3389/fgene.2022.819699
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author He, Binjun
Zhang, Kang
Han, Xiaoliang
Su, Chao
Zhao, Jiaming
Wang, Guoxia
Wang, Guzong
Zhang, Liuya
Hu, Wenbin
author_facet He, Binjun
Zhang, Kang
Han, Xiaoliang
Su, Chao
Zhao, Jiaming
Wang, Guoxia
Wang, Guzong
Zhang, Liuya
Hu, Wenbin
author_sort He, Binjun
collection PubMed
description Objective: Esophageal squamous cell carcinoma (ESCC) presents high morbidity and mortality. It was demonstrated that blood-derived vesicles can facilitate ESCC development and transmit regulating signals. However, the molecular mechanism of vesicle miRNA secreted by tumor cells affecting ESCC progression has not been explored. Methods: The mRNA-related signaling pathways and differentially expressed genes were screened out in TCGA dataset. The levels of miRNA-105-5p and SPARCL1 were determined by qRT-PCR. Protein level determination was processed using Western blot. The interaction between the two genes was verified with the dual-luciferase method. A transmission electron microscope was utilized to further identify extracellular vesicles (EVs), and co-culture assay was performed to validate the intake of EVs. In vitro experiments were conducted to evaluate cell function changes in ESCC. A mice tumor formation experiment was carried out to observe tumor growth in vivo. Results: MiRNA-105-5p expression was increased in ESCC, while SPARCL1 was less expressed. MiRNA-105-5p facilitated cell behaviors in ESCC through targeting SPARCL1 and regulating the focal adhesion kinase (FAK)/Akt signaling pathway. Blood-derived external vesicles containing miRNA-105-5p and EVs could be internalized by ESCC cells. Then, miRNA-105-5p could be transferred to ESCC cells to foster tumorigenesis as well as cell behaviors. Conclusion: EV-carried miRNA-105-5p entered ESCC cells and promoted tumor-relevant functions by mediating SPARCL1 and the FAK/Akt signaling pathway, which indicated that the treatment of ESCC via serum EVs might be a novel therapy and that miRNA-105-5p can be a molecular target for ESCC therapy.
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spelling pubmed-89277242022-03-18 Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway He, Binjun Zhang, Kang Han, Xiaoliang Su, Chao Zhao, Jiaming Wang, Guoxia Wang, Guzong Zhang, Liuya Hu, Wenbin Front Genet Genetics Objective: Esophageal squamous cell carcinoma (ESCC) presents high morbidity and mortality. It was demonstrated that blood-derived vesicles can facilitate ESCC development and transmit regulating signals. However, the molecular mechanism of vesicle miRNA secreted by tumor cells affecting ESCC progression has not been explored. Methods: The mRNA-related signaling pathways and differentially expressed genes were screened out in TCGA dataset. The levels of miRNA-105-5p and SPARCL1 were determined by qRT-PCR. Protein level determination was processed using Western blot. The interaction between the two genes was verified with the dual-luciferase method. A transmission electron microscope was utilized to further identify extracellular vesicles (EVs), and co-culture assay was performed to validate the intake of EVs. In vitro experiments were conducted to evaluate cell function changes in ESCC. A mice tumor formation experiment was carried out to observe tumor growth in vivo. Results: MiRNA-105-5p expression was increased in ESCC, while SPARCL1 was less expressed. MiRNA-105-5p facilitated cell behaviors in ESCC through targeting SPARCL1 and regulating the focal adhesion kinase (FAK)/Akt signaling pathway. Blood-derived external vesicles containing miRNA-105-5p and EVs could be internalized by ESCC cells. Then, miRNA-105-5p could be transferred to ESCC cells to foster tumorigenesis as well as cell behaviors. Conclusion: EV-carried miRNA-105-5p entered ESCC cells and promoted tumor-relevant functions by mediating SPARCL1 and the FAK/Akt signaling pathway, which indicated that the treatment of ESCC via serum EVs might be a novel therapy and that miRNA-105-5p can be a molecular target for ESCC therapy. Frontiers Media S.A. 2022-03-03 /pmc/articles/PMC8927724/ /pubmed/35309127 http://dx.doi.org/10.3389/fgene.2022.819699 Text en Copyright © 2022 He, Zhang, Han, Su, Zhao, Wang, Wang, Zhang and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
He, Binjun
Zhang, Kang
Han, Xiaoliang
Su, Chao
Zhao, Jiaming
Wang, Guoxia
Wang, Guzong
Zhang, Liuya
Hu, Wenbin
Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway
title Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway
title_full Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway
title_fullStr Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway
title_full_unstemmed Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway
title_short Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway
title_sort extracellular vesicle-derived mir-105-5p promotes malignant phenotypes of esophageal squamous cell carcinoma by targeting sparcl1 via fak/akt signaling pathway
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927724/
https://www.ncbi.nlm.nih.gov/pubmed/35309127
http://dx.doi.org/10.3389/fgene.2022.819699
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