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Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7

BACKGROUND: Glioma is one of the most common central nervous system malignant tumors, accounting for 45~60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy. METHODS: Long non-c...

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Autores principales: Zhang, Ruijie, Li, Peng, Lv, Heli, Li, Nana, Ren, Suliang, Xu, Wentao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207674/
https://www.ncbi.nlm.nih.gov/pubmed/34134771
http://dx.doi.org/10.1186/s13287-021-02393-8
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author Zhang, Ruijie
Li, Peng
Lv, Heli
Li, Nana
Ren, Suliang
Xu, Wentao
author_facet Zhang, Ruijie
Li, Peng
Lv, Heli
Li, Nana
Ren, Suliang
Xu, Wentao
author_sort Zhang, Ruijie
collection PubMed
description BACKGROUND: Glioma is one of the most common central nervous system malignant tumors, accounting for 45~60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy. METHODS: Long non-coding RNA (lncRNA) SNHG16 expression level was measured by microarray and qRT-PCR assay; ISH was used to identify the location of SNHG16. Cancer stem cells (CSCs) were separated from glioma tissues and identified using immunofluorescence. Exosomes were isolated from CSCs and cancer cells and identified by TEM and western blot. MTT, wound healing, transwell, and colony formation assay were performed to explore the role of SNHG16 or si-SNHG16 from CSCs on progression of glioma cells. RIP was used to verify the interaction between SNHG16 and TLR7. The experiment of Xenograft used for exploring the function of SNHG16/ TLR7/MyD88/NFκB/c-Myc on growth on glioma in vivo. RESULTS: Microarray assay showed long non-coding RNA (lncRNA) SNHG16 was upregulated in glioma. Followed qRT-PCR also showed an increase of SNHG16 in glioma tissues; high expression of SNHG16 indicated a poor prognosis in glioma patients. Interestingly, SNHG16 was packaged into exosomes and derived from CSCs. Functional analysis showed exo-SNHG16 secreted by CSCs promoted the progression of glioma cell lines SHG44 and U251. Furthermore, SNHG16 interacted with TLR7 and activated NFκB/c-Myc signaling in glioma cells. And the silencing of TLR7 inhibited the progression of SHG44 and U251 cells by exo-SNHG16 from CSCs. In vivo tumorigenesis experiments showed that exo-SNHG16 induced glioma progression by activating TLR7/MyD88/NFκB/c-Myc signaling. CONCLUSION: Our study suggested CSC-derived exo-SNHG16 promoted cancer progression by activating TLR7/MyD88/NFκB/c-Myc signaling pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02393-8.
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spelling pubmed-82076742021-06-16 Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7 Zhang, Ruijie Li, Peng Lv, Heli Li, Nana Ren, Suliang Xu, Wentao Stem Cell Res Ther Research BACKGROUND: Glioma is one of the most common central nervous system malignant tumors, accounting for 45~60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy. METHODS: Long non-coding RNA (lncRNA) SNHG16 expression level was measured by microarray and qRT-PCR assay; ISH was used to identify the location of SNHG16. Cancer stem cells (CSCs) were separated from glioma tissues and identified using immunofluorescence. Exosomes were isolated from CSCs and cancer cells and identified by TEM and western blot. MTT, wound healing, transwell, and colony formation assay were performed to explore the role of SNHG16 or si-SNHG16 from CSCs on progression of glioma cells. RIP was used to verify the interaction between SNHG16 and TLR7. The experiment of Xenograft used for exploring the function of SNHG16/ TLR7/MyD88/NFκB/c-Myc on growth on glioma in vivo. RESULTS: Microarray assay showed long non-coding RNA (lncRNA) SNHG16 was upregulated in glioma. Followed qRT-PCR also showed an increase of SNHG16 in glioma tissues; high expression of SNHG16 indicated a poor prognosis in glioma patients. Interestingly, SNHG16 was packaged into exosomes and derived from CSCs. Functional analysis showed exo-SNHG16 secreted by CSCs promoted the progression of glioma cell lines SHG44 and U251. Furthermore, SNHG16 interacted with TLR7 and activated NFκB/c-Myc signaling in glioma cells. And the silencing of TLR7 inhibited the progression of SHG44 and U251 cells by exo-SNHG16 from CSCs. In vivo tumorigenesis experiments showed that exo-SNHG16 induced glioma progression by activating TLR7/MyD88/NFκB/c-Myc signaling. CONCLUSION: Our study suggested CSC-derived exo-SNHG16 promoted cancer progression by activating TLR7/MyD88/NFκB/c-Myc signaling pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02393-8. BioMed Central 2021-06-16 /pmc/articles/PMC8207674/ /pubmed/34134771 http://dx.doi.org/10.1186/s13287-021-02393-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhang, Ruijie
Li, Peng
Lv, Heli
Li, Nana
Ren, Suliang
Xu, Wentao
Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7
title Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7
title_full Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7
title_fullStr Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7
title_full_unstemmed Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7
title_short Exosomal SNHG16 secreted by CSCs promotes glioma development via TLR7
title_sort exosomal snhg16 secreted by cscs promotes glioma development via tlr7
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207674/
https://www.ncbi.nlm.nih.gov/pubmed/34134771
http://dx.doi.org/10.1186/s13287-021-02393-8
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