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Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis

Gastric cancer (GC) is a heterogeneous disease with poor prognosis. Tumor-derived extracellular vesicles (EVs) assume a role in intercellular communication by carrying various molecules, including proteins, RNA, and DNAs, which has been identified to exhibit oncogenic effect in GC. Therefore, this r...

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Autores principales: Li, Bopei, Chen, Yeyang, Liang, Liang, Wang, Ye, Huang, Weijia, Zhao, Kun, Liu, Siyu, Deng, Guofei, Chen, Junqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904444/
https://www.ncbi.nlm.nih.gov/pubmed/35260554
http://dx.doi.org/10.1038/s41419-021-04446-5
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author Li, Bopei
Chen, Yeyang
Liang, Liang
Wang, Ye
Huang, Weijia
Zhao, Kun
Liu, Siyu
Deng, Guofei
Chen, Junqiang
author_facet Li, Bopei
Chen, Yeyang
Liang, Liang
Wang, Ye
Huang, Weijia
Zhao, Kun
Liu, Siyu
Deng, Guofei
Chen, Junqiang
author_sort Li, Bopei
collection PubMed
description Gastric cancer (GC) is a heterogeneous disease with poor prognosis. Tumor-derived extracellular vesicles (EVs) assume a role in intercellular communication by carrying various molecules, including proteins, RNA, and DNAs, which has been identified to exhibit oncogenic effect in GC. Therefore, this research aimed to figure out whether tumor-derived EVs transmit c-Myc to orchestrate the growth and metastasis of GC. KCNQ1OT1, microRNA (miR)-556-3p and CLIC1 expression of GC tissues was detected through RT-qPCR. EVs were isolated from GC cells, followed by RT-qPCR and Western blot analysis of c-Myc expression in EVs and GC cells. Next, GC cells were incubated with EVs or transfected with a series of mimic, inhibitor, or siRNAs to assess their effects on cell viability, migrative, invasive, and apoptotic potential. Relationship among c-Myc, KCNQ1OT1, miR-556-3p, and CLIC1 was evaluated by dual-luciferase reporter assay. PI3K/AKT pathway-related proteins were assessed through Western blot analysis. KCNQ1OT1 and CLIC1 were highly expressed but miR-556-3p in GC tissues. c-Myc was high-expressed in tumor-derived EVs and GC cells. Mechanistically, c-Myc could induce KCNQ1OT1 expression, and KCNQ1OT1 bound to miR-556-3p that negatively targeted CLIC1 to inactivate PI3K/AKT pathway. Tumor-derived EVs, EVs-c-Myc, KCNQ1OT1 or CLIC1 overexpression, or miR-556-3p inhibition promoted GC cell proliferative, invasive, and migrative capacities but repressed their apoptosis through activating PI3K/AKT pathway. Collectively, tumor-derived EVs carrying c-Myc activated KCNQ1OT1 to downregulate miR-556-3p, thus elevating CLIC1 expression to activate the PI3K/AKT pathway, which facilitated the growth and metastasis of GC.
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spelling pubmed-89044442022-03-23 Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis Li, Bopei Chen, Yeyang Liang, Liang Wang, Ye Huang, Weijia Zhao, Kun Liu, Siyu Deng, Guofei Chen, Junqiang Cell Death Dis Article Gastric cancer (GC) is a heterogeneous disease with poor prognosis. Tumor-derived extracellular vesicles (EVs) assume a role in intercellular communication by carrying various molecules, including proteins, RNA, and DNAs, which has been identified to exhibit oncogenic effect in GC. Therefore, this research aimed to figure out whether tumor-derived EVs transmit c-Myc to orchestrate the growth and metastasis of GC. KCNQ1OT1, microRNA (miR)-556-3p and CLIC1 expression of GC tissues was detected through RT-qPCR. EVs were isolated from GC cells, followed by RT-qPCR and Western blot analysis of c-Myc expression in EVs and GC cells. Next, GC cells were incubated with EVs or transfected with a series of mimic, inhibitor, or siRNAs to assess their effects on cell viability, migrative, invasive, and apoptotic potential. Relationship among c-Myc, KCNQ1OT1, miR-556-3p, and CLIC1 was evaluated by dual-luciferase reporter assay. PI3K/AKT pathway-related proteins were assessed through Western blot analysis. KCNQ1OT1 and CLIC1 were highly expressed but miR-556-3p in GC tissues. c-Myc was high-expressed in tumor-derived EVs and GC cells. Mechanistically, c-Myc could induce KCNQ1OT1 expression, and KCNQ1OT1 bound to miR-556-3p that negatively targeted CLIC1 to inactivate PI3K/AKT pathway. Tumor-derived EVs, EVs-c-Myc, KCNQ1OT1 or CLIC1 overexpression, or miR-556-3p inhibition promoted GC cell proliferative, invasive, and migrative capacities but repressed their apoptosis through activating PI3K/AKT pathway. Collectively, tumor-derived EVs carrying c-Myc activated KCNQ1OT1 to downregulate miR-556-3p, thus elevating CLIC1 expression to activate the PI3K/AKT pathway, which facilitated the growth and metastasis of GC. Nature Publishing Group UK 2022-03-08 /pmc/articles/PMC8904444/ /pubmed/35260554 http://dx.doi.org/10.1038/s41419-021-04446-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Bopei
Chen, Yeyang
Liang, Liang
Wang, Ye
Huang, Weijia
Zhao, Kun
Liu, Siyu
Deng, Guofei
Chen, Junqiang
Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis
title Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis
title_full Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis
title_fullStr Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis
title_full_unstemmed Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis
title_short Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis
title_sort tumor-derived extracellular vesicles shuttle c-myc to promote gastric cancer growth and metastasis via the kcnq1ot1/mir-556-3p/clic1 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904444/
https://www.ncbi.nlm.nih.gov/pubmed/35260554
http://dx.doi.org/10.1038/s41419-021-04446-5
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