Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain.
Lung Cancer Cell-Derived Exosomal let-7d-5p Down-Regulates OPRM1 to Promote Cancer-Induced Bone Pain.
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肺癌细胞衍生的外泌体let-7d-5p下调OPRM1以促进癌症引起的骨痛
DOI：
10.3389/fcell.2021.666857
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发表时间：
2021
影响因子：
5.5
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Li X;Chen Y;Wang J;Jiang C;Huang Y
癌性骨痛（CIBP）是恶性肿瘤向骨转移引起的疼痛，占所有慢性癌性疼痛的一半以上，严重影响肿瘤患者的生活质量。高达40%的晚期肺癌患者患有CIBP。MicroRNA （miRNA）通过外泌体在细胞间传递，介导细胞间通讯，并发挥多种生物学功能。研究表明，癌症分泌的miRNA可以改变肿瘤微环境，但外泌体介导的miRNA转移是否在CIBP中发挥作用尚不清楚。本研究中，外泌体来源的A549细胞和NCI-H1299细胞中15种miRNAs和18种miRNAs的表达水平均显著上调，qRT-PCR进一步证实let-7d-5p的表达水平升高最为显著。在体外，外泌体let-7d-5p （EXO let-7d-5p）可被背根神经节（DRG）神经元摄取，抑制靶基因阿片受体mu 1 （OPRM1）的蛋白水平。进一步证实EXO let-7d-5p参与体内CIBP的产生和维持。我们的研究结果阐明了EXO let-7d-5p抑制OPRM1导致CIBP的分子机制，为CIBP的防治提供了新的线索和干预靶点。
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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影响因子：
5.1
作者：
Ke, Changbin;Gao, Feng;Tian, Yuke
通讯作者：
Tian, Yuke
影响因子：
2.9
作者：
Zhang, Honghong;Xu, Sijuan;Liu, Xiaoli
通讯作者：
Liu, Xiaoli
miRNA-23a/CXCR4通过直接靶向TXNIP/NLRP3炎性体轴调节神经性疼痛
影响因子：
9.3
作者：
Pan Z;Shan Q;Gu P;Wang XM;Tai LW;Sun M;Luo X;Sun L;Cheung CW
通讯作者：
Cheung CW
影响因子：
15.9
作者：
Laedermann, Cedric J.;Cachemaille, Matthieu;Decosterd, Isabelle
通讯作者：
Decosterd, Isabelle
影响因子：
3.7
作者：
Uhr, Katharina;Prager-van der Smissen, Wendy J. C.;Martens, John W. M.
通讯作者：
Martens, John W. M.