Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

Bone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTH...

Descripción completa

Detalles Bibliográficos
Autores principales: Ni, Jianjiao, Zhang, Xiaofei, Li, Juan, Zheng, Zhiqin, Zhang, Junhua, Zhao, Weixin, Liu, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253828/
https://www.ncbi.nlm.nih.gov/pubmed/34215717
http://dx.doi.org/10.1038/s41419-021-03928-w
_version_ 1783717599239995392
author Ni, Jianjiao
Zhang, Xiaofei
Li, Juan
Zheng, Zhiqin
Zhang, Junhua
Zhao, Weixin
Liu, Liang
author_facet Ni, Jianjiao
Zhang, Xiaofei
Li, Juan
Zheng, Zhiqin
Zhang, Junhua
Zhao, Weixin
Liu, Liang
author_sort Ni, Jianjiao
collection PubMed
description Bone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.
format Online
Article
Text
id pubmed-8253828
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-82538282021-07-20 Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts Ni, Jianjiao Zhang, Xiaofei Li, Juan Zheng, Zhiqin Zhang, Junhua Zhao, Weixin Liu, Liang Cell Death Dis Article Bone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC. Nature Publishing Group UK 2021-07-02 /pmc/articles/PMC8253828/ /pubmed/34215717 http://dx.doi.org/10.1038/s41419-021-03928-w Text en © The Author(s) 2021, corrected publication 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
Ni, Jianjiao
Zhang, Xiaofei
Li, Juan
Zheng, Zhiqin
Zhang, Junhua
Zhao, Weixin
Liu, Liang
Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts
title Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts
title_full Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts
title_fullStr Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts
title_full_unstemmed Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts
title_short Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts
title_sort tumour-derived exosomal lncrna-sox2ot promotes bone metastasis of non-small cell lung cancer by targeting the mirna-194-5p/rac1 signalling axis in osteoclasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253828/
https://www.ncbi.nlm.nih.gov/pubmed/34215717
http://dx.doi.org/10.1038/s41419-021-03928-w
work_keys_str_mv AT nijianjiao tumourderivedexosomallncrnasox2otpromotesbonemetastasisofnonsmallcelllungcancerbytargetingthemirna1945prac1signallingaxisinosteoclasts
AT zhangxiaofei tumourderivedexosomallncrnasox2otpromotesbonemetastasisofnonsmallcelllungcancerbytargetingthemirna1945prac1signallingaxisinosteoclasts
AT lijuan tumourderivedexosomallncrnasox2otpromotesbonemetastasisofnonsmallcelllungcancerbytargetingthemirna1945prac1signallingaxisinosteoclasts
AT zhengzhiqin tumourderivedexosomallncrnasox2otpromotesbonemetastasisofnonsmallcelllungcancerbytargetingthemirna1945prac1signallingaxisinosteoclasts
AT zhangjunhua tumourderivedexosomallncrnasox2otpromotesbonemetastasisofnonsmallcelllungcancerbytargetingthemirna1945prac1signallingaxisinosteoclasts
AT zhaoweixin tumourderivedexosomallncrnasox2otpromotesbonemetastasisofnonsmallcelllungcancerbytargetingthemirna1945prac1signallingaxisinosteoclasts
AT liuliang tumourderivedexosomallncrnasox2otpromotesbonemetastasisofnonsmallcelllungcancerbytargetingthemirna1945prac1signallingaxisinosteoclasts

Ejemplares similares