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Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway

Increasing evidence indicates that lymphocyte cytosolic protein 1 (LCP1) overexpression contributes to tumor progression; however, its role in osteosarcoma (OS) remains unclear. We aimed to investigate the potential effect of LCP1 in OS and the underlying mechanisms. We first demonstrated that LCP1...

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Autores principales: Ge, Xuhui, Liu, Wei, Zhao, Wene, Feng, Shuang, Duan, Ao, Ji, Chengyue, Shen, Kai, Liu, Wanshun, Zhou, Jiawen, Jiang, Dongdong, Rong, Yuluo, Gong, Fangyi, Wang, Jiaxing, Xu, Zhiyang, Li, Xiaoyan, Fan, Jin, Wei, Yongzhong, Bai, Jianling, Cai, Weihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452114/
https://www.ncbi.nlm.nih.gov/pubmed/32810692
http://dx.doi.org/10.1016/j.omtn.2020.07.025
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author Ge, Xuhui
Liu, Wei
Zhao, Wene
Feng, Shuang
Duan, Ao
Ji, Chengyue
Shen, Kai
Liu, Wanshun
Zhou, Jiawen
Jiang, Dongdong
Rong, Yuluo
Gong, Fangyi
Wang, Jiaxing
Xu, Zhiyang
Li, Xiaoyan
Fan, Jin
Wei, Yongzhong
Bai, Jianling
Cai, Weihua
author_facet Ge, Xuhui
Liu, Wei
Zhao, Wene
Feng, Shuang
Duan, Ao
Ji, Chengyue
Shen, Kai
Liu, Wanshun
Zhou, Jiawen
Jiang, Dongdong
Rong, Yuluo
Gong, Fangyi
Wang, Jiaxing
Xu, Zhiyang
Li, Xiaoyan
Fan, Jin
Wei, Yongzhong
Bai, Jianling
Cai, Weihua
author_sort Ge, Xuhui
collection PubMed
description Increasing evidence indicates that lymphocyte cytosolic protein 1 (LCP1) overexpression contributes to tumor progression; however, its role in osteosarcoma (OS) remains unclear. We aimed to investigate the potential effect of LCP1 in OS and the underlying mechanisms. We first demonstrated that LCP1 is upregulated in OS cell lines and tissues. Then, we found that aberrant expression of LCP1 could induce the proliferation and metastasis of OS cells in vitro and in vivo by destabilizing neuregulin receptor degradation protein-1 (Nrdp1) and subsequently activating the JAK2/STAT3 signaling pathway. When coculturing OS cells with bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, we validated that oncogenic LCP1 in OS was transferred from BMSCs via exosomes. Moreover, microRNA (miR)-135a-5p, a tumor suppressor, was found to interact upstream of LCP1 to counteract the pro-tumorigenesis effects of LCP1 in OS. In conclusion, BMSC-derived exosomal LCP1 promotes OS proliferation and metastasis via the JAK2/STAT3 pathway. Targeting the miR-135a-5p/LCP1 axis may have potential in treating OS.
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spelling pubmed-74521142020-09-09 Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway Ge, Xuhui Liu, Wei Zhao, Wene Feng, Shuang Duan, Ao Ji, Chengyue Shen, Kai Liu, Wanshun Zhou, Jiawen Jiang, Dongdong Rong, Yuluo Gong, Fangyi Wang, Jiaxing Xu, Zhiyang Li, Xiaoyan Fan, Jin Wei, Yongzhong Bai, Jianling Cai, Weihua Mol Ther Nucleic Acids Article Increasing evidence indicates that lymphocyte cytosolic protein 1 (LCP1) overexpression contributes to tumor progression; however, its role in osteosarcoma (OS) remains unclear. We aimed to investigate the potential effect of LCP1 in OS and the underlying mechanisms. We first demonstrated that LCP1 is upregulated in OS cell lines and tissues. Then, we found that aberrant expression of LCP1 could induce the proliferation and metastasis of OS cells in vitro and in vivo by destabilizing neuregulin receptor degradation protein-1 (Nrdp1) and subsequently activating the JAK2/STAT3 signaling pathway. When coculturing OS cells with bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, we validated that oncogenic LCP1 in OS was transferred from BMSCs via exosomes. Moreover, microRNA (miR)-135a-5p, a tumor suppressor, was found to interact upstream of LCP1 to counteract the pro-tumorigenesis effects of LCP1 in OS. In conclusion, BMSC-derived exosomal LCP1 promotes OS proliferation and metastasis via the JAK2/STAT3 pathway. Targeting the miR-135a-5p/LCP1 axis may have potential in treating OS. American Society of Gene & Cell Therapy 2020-07-23 /pmc/articles/PMC7452114/ /pubmed/32810692 http://dx.doi.org/10.1016/j.omtn.2020.07.025 Text en © 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Ge, Xuhui
Liu, Wei
Zhao, Wene
Feng, Shuang
Duan, Ao
Ji, Chengyue
Shen, Kai
Liu, Wanshun
Zhou, Jiawen
Jiang, Dongdong
Rong, Yuluo
Gong, Fangyi
Wang, Jiaxing
Xu, Zhiyang
Li, Xiaoyan
Fan, Jin
Wei, Yongzhong
Bai, Jianling
Cai, Weihua
Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway
title Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway
title_full Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway
title_fullStr Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway
title_full_unstemmed Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway
title_short Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway
title_sort exosomal transfer of lcp1 promotes osteosarcoma cell tumorigenesis and metastasis by activating the jak2/stat3 signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452114/
https://www.ncbi.nlm.nih.gov/pubmed/32810692
http://dx.doi.org/10.1016/j.omtn.2020.07.025
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