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Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain

Cancer-induced bone pain (CIBP) is the pain caused by metastasis of malignant tumors to the bone, accounting for more than half of all chronic cancer pain, which seriously affects the quality of life among tumor patients. Up to 40% of patients with advanced lung cancer suffer from CIBP. MicroRNA (mi...

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Autores principales: Li, Xihan, Chen, Yu, Wang, Jialun, Jiang, Chengfei, Huang, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188355/
https://www.ncbi.nlm.nih.gov/pubmed/34124049
http://dx.doi.org/10.3389/fcell.2021.666857
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author Li, Xihan
Chen, Yu
Wang, Jialun
Jiang, Chengfei
Huang, Ying
author_facet Li, Xihan
Chen, Yu
Wang, Jialun
Jiang, Chengfei
Huang, Ying
author_sort Li, Xihan
collection PubMed
description Cancer-induced bone pain (CIBP) is the pain caused by metastasis of malignant tumors to the bone, accounting for more than half of all chronic cancer pain, which seriously affects the quality of life among tumor patients. Up to 40% of patients with advanced lung cancer suffer from CIBP. MicroRNA (miRNA) transfers between cells through exosomes, mediates cell-to-cell communication, and performs various biological functions. Studies have shown that miRNAs secreted by cancer can modify the tumor microenvironment, but whether exosome-mediated miRNA transfer plays a role in CIBP is still unknown. In this study, the expression levels of 15 miRNAs in exosomes derived A549 cells and 18 miRNAs in exosomes derived NCI-H1299 cells were significantly up-regulated, and qRT-PCR further confirmed that the level of let-7d-5p was increased most considerably. In vitro, exosomal let-7d-5p (EXO let-7d-5p) can be taken up by dorsal root ganglion (DRG) neurons and inhibit the protein level of the target gene opioid receptor mu 1 (OPRM1). EXO let-7d-5p was further confirmed to be involved in the generation and maintenance of CIBP in vivo. Our findings clarify the molecular mechanism of CIBP caused by the inhibition of OPRM1 by EXO let-7d-5p, providing new clues and intervention targets for the prevention and treatment of CIBP.
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spelling pubmed-81883552021-06-10 Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain Li, Xihan Chen, Yu Wang, Jialun Jiang, Chengfei Huang, Ying Front Cell Dev Biol Cell and Developmental Biology Cancer-induced bone pain (CIBP) is the pain caused by metastasis of malignant tumors to the bone, accounting for more than half of all chronic cancer pain, which seriously affects the quality of life among tumor patients. Up to 40% of patients with advanced lung cancer suffer from CIBP. MicroRNA (miRNA) transfers between cells through exosomes, mediates cell-to-cell communication, and performs various biological functions. Studies have shown that miRNAs secreted by cancer can modify the tumor microenvironment, but whether exosome-mediated miRNA transfer plays a role in CIBP is still unknown. In this study, the expression levels of 15 miRNAs in exosomes derived A549 cells and 18 miRNAs in exosomes derived NCI-H1299 cells were significantly up-regulated, and qRT-PCR further confirmed that the level of let-7d-5p was increased most considerably. In vitro, exosomal let-7d-5p (EXO let-7d-5p) can be taken up by dorsal root ganglion (DRG) neurons and inhibit the protein level of the target gene opioid receptor mu 1 (OPRM1). EXO let-7d-5p was further confirmed to be involved in the generation and maintenance of CIBP in vivo. Our findings clarify the molecular mechanism of CIBP caused by the inhibition of OPRM1 by EXO let-7d-5p, providing new clues and intervention targets for the prevention and treatment of CIBP. Frontiers Media S.A. 2021-05-26 /pmc/articles/PMC8188355/ /pubmed/34124049 http://dx.doi.org/10.3389/fcell.2021.666857 Text en Copyright © 2021 Li, Chen, Wang, Jiang and Huang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Li, Xihan
Chen, Yu
Wang, Jialun
Jiang, Chengfei
Huang, Ying
Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain
title Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain
title_full Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain
title_fullStr Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain
title_full_unstemmed Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain
title_short Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain
title_sort lung cancer cell-derived exosomal let-7d-5p down-regulates oprm1 to promote cancer-induced bone pain
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188355/
https://www.ncbi.nlm.nih.gov/pubmed/34124049
http://dx.doi.org/10.3389/fcell.2021.666857
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