| Autor: |
Mei-Xin Li, Sheng Hu, He-Hua Lei, Meng Yuan, Xu Li, Wen-Kui Hou, Xiang-Jie Huang, Bing-Wen Xiao, Teng-Xiang Yu, Xiao-Hui Zhang, Xiao-Ting Wu, Wen-Qiang Jing, Hyeon-Jeong Lee, Juan-Juan Li, Da Fu, Li-Min Zhang, Wei Yan |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-20 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-54706-z |
| Popis: |
Abstract Cancer cells secrete extracellular vesicles (EV) encapsulating bioactive cargoes to facilitate inter-organ communication in vivo and are emerging as critical mediators of tumor progression and metastasis, a condition which is often accompanied by a dysregulated cholesterol metabolism. Whether EVs are involved in the control of cholesterol homeostasis during tumor metastasis is still undefined and warrant further investigation. Here, we find that breast cancer-derived exosomal miR-9-5p induces the expression of HMGCR and CH25H, two enzymes involved in cholesterol synthesis and the conversion of 25-hydroxycholesterol from cholesterol by targeting INSIG1, INSIG2 and ATF3 genes in the liver. Notably, in vivo miR-9-5p antagomir treatment and genetic CH25H ablation prevents tumor metastasis in a mouse model of breast cancer. Thus, our findings reveal the regulatory mechanism of tumor-derived miR-9-5p in liver metastasis by linking oxysterol metabolism and Kupffer cell polarization, shedding light on future applications for cancer diagnosis and treatment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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