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Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer

BACKGROUND: Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (G...

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Autores principales: Zhang, Yan, Chen, Lin, Ye, Xuanting, Wu, Zhixiong, Zhang, Zeyu, Sun, Biaofeng, Fu, Hong, Fu, Chuangang, Liang, Xiaofei, Jiang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111998/
https://www.ncbi.nlm.nih.gov/pubmed/33971889
http://dx.doi.org/10.1186/s12951-021-00873-w
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author Zhang, Yan
Chen, Lin
Ye, Xuanting
Wu, Zhixiong
Zhang, Zeyu
Sun, Biaofeng
Fu, Hong
Fu, Chuangang
Liang, Xiaofei
Jiang, Hong
author_facet Zhang, Yan
Chen, Lin
Ye, Xuanting
Wu, Zhixiong
Zhang, Zeyu
Sun, Biaofeng
Fu, Hong
Fu, Chuangang
Liang, Xiaofei
Jiang, Hong
author_sort Zhang, Yan
collection PubMed
description BACKGROUND: Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC. RESULTS: The prepared CD63 immunomagnetic beads (CD63-IMB) had the characteristics of good dispersity and high magnetic response. The isolated exosomes were presented with elliptical membranous particles under a transmission electron microscope (TEM), with the particle size of 89.78 ± 4.8 nm. Western blot (WB) results showed that the exosomes were rich in CD9 and CD81. The Dil-labeled exosomes were distributed around cytoplasm and nucleus of cells by imaging flow cytometry (IFC) analysis. The results of quantitative real-time PCR (qRT-PCR) revealed that the FRLnc1 expressions were up-regulated in GC cells, tumor tissues, and serum of GC patients. An obviously up-regulated FRLnc1 expression was found in serum exosomes of GC patients. Up-regulation of FRLnc1 expression was closely correlated to lymph node metastasis (LNM) and TNM stage with the combination of relevant clinicopathological parameter analysis. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell proliferation and migration in HGC-27 cells, whereas FRLnc1 overexpression promoted cell proliferation and migration in MKN45 cells. After exosome treatment, the FRLnc1 expression was significantly increased in MKN45 cells, and the MKN45 cells showed increased ability of proliferation and migration. CONCLUSION: GC cells-derived exosomes played roles in promoting the growth and metastasis of GC by transporting FRLnc1, suggesting that FRLnc1 in the exosomes may be a potential biomarker for the diagnosis and treatment of GC. The delivery of FRLnc1 by the exosomes may provide a new way for the treatment of GC. Trial registration 2020-KYSB-094. Registered 23 March 2020—Retrospectively registered GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00873-w.
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spelling pubmed-81119982021-05-11 Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer Zhang, Yan Chen, Lin Ye, Xuanting Wu, Zhixiong Zhang, Zeyu Sun, Biaofeng Fu, Hong Fu, Chuangang Liang, Xiaofei Jiang, Hong J Nanobiotechnology Research BACKGROUND: Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC. RESULTS: The prepared CD63 immunomagnetic beads (CD63-IMB) had the characteristics of good dispersity and high magnetic response. The isolated exosomes were presented with elliptical membranous particles under a transmission electron microscope (TEM), with the particle size of 89.78 ± 4.8 nm. Western blot (WB) results showed that the exosomes were rich in CD9 and CD81. The Dil-labeled exosomes were distributed around cytoplasm and nucleus of cells by imaging flow cytometry (IFC) analysis. The results of quantitative real-time PCR (qRT-PCR) revealed that the FRLnc1 expressions were up-regulated in GC cells, tumor tissues, and serum of GC patients. An obviously up-regulated FRLnc1 expression was found in serum exosomes of GC patients. Up-regulation of FRLnc1 expression was closely correlated to lymph node metastasis (LNM) and TNM stage with the combination of relevant clinicopathological parameter analysis. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell proliferation and migration in HGC-27 cells, whereas FRLnc1 overexpression promoted cell proliferation and migration in MKN45 cells. After exosome treatment, the FRLnc1 expression was significantly increased in MKN45 cells, and the MKN45 cells showed increased ability of proliferation and migration. CONCLUSION: GC cells-derived exosomes played roles in promoting the growth and metastasis of GC by transporting FRLnc1, suggesting that FRLnc1 in the exosomes may be a potential biomarker for the diagnosis and treatment of GC. The delivery of FRLnc1 by the exosomes may provide a new way for the treatment of GC. Trial registration 2020-KYSB-094. Registered 23 March 2020—Retrospectively registered GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00873-w. BioMed Central 2021-05-10 /pmc/articles/PMC8111998/ /pubmed/33971889 http://dx.doi.org/10.1186/s12951-021-00873-w 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, Yan
Chen, Lin
Ye, Xuanting
Wu, Zhixiong
Zhang, Zeyu
Sun, Biaofeng
Fu, Hong
Fu, Chuangang
Liang, Xiaofei
Jiang, Hong
Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer
title Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer
title_full Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer
title_fullStr Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer
title_full_unstemmed Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer
title_short Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer
title_sort expression and mechanism of exosome-mediated a foxm1 related long noncoding rna in gastric cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111998/
https://www.ncbi.nlm.nih.gov/pubmed/33971889
http://dx.doi.org/10.1186/s12951-021-00873-w
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