期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.666857
关键词
exosome; miRNA; let-7d-5p; OPRM1; cancer-induced bone pain
资金
- National Natural Science Foundation of China [81801100, 81972879]
- Natural Science Foundation of Jiangsu Province [BK20180130]
- Science and Technology Program of Nanjing [201803037]
- Fundamental Research Funds for the Central Universities [021414380449]
Cancer-induced bone pain (CIBP) is a serious condition affecting the quality of life among tumor patients, with miRNA potentially playing a role in its development and maintenance, particularly let-7d-5p.
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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