MiR-629-5p promotes the invasion of lung adenocarcinoma via increasing both tumor cell invasion and endothelial cell permeability
| العنوان: | MiR-629-5p promotes the invasion of lung adenocarcinoma via increasing both tumor cell invasion and endothelial cell permeability |
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| المؤلفون: | Huibiao Zhang, Jin Ren, Chao Peng, Yizheng Wang, Ruimin Huang, Liting Zhao, Zhouteng Tao, Yuxiang Chen, Henglei Lu, Jiahui Mou, Yue Yin, Lei Fan, Jing Chen, Xinming Qi, Yu Li |
| المصدر: | Oncogene. 39:3473-3488 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Lung Neoplasms, Motility, Adenocarcinoma of Lung, Biology, Permeability, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Biomarkers, Tumor, Genetics, medicine, Humans, Neoplasm Invasiveness, RNA, Neoplasm, Lung cancer, Molecular Biology, A549 cell, Cadherin, HEK 293 cells, Endothelial Cells, Cadherins, medicine.disease, Neoplasm Proteins, Endothelial stem cell, MicroRNAs, HEK293 Cells, 030104 developmental biology, A549 Cells, 030220 oncology & carcinogenesis, Cancer research, Adenocarcinoma |
| الوصف: | Tumor invasion underlies further metastasis, the leading cause for cancer-related deaths. Deregulation of microRNAs has been identified associated with the malignant behavior of various cancers, including lung adenocarcinoma (LUAD), the major subtype of lung cancer. Here, we showed the significantly positive correlation between miR-629-5p level and tumor invasion in LUAD specimens (n = 49). In a human LUAD metastasis mouse model, H1650 cells (high level of miR-629-5p) were more aggressive than A549 cells (low level of miR-629-5p) in vivo, including higher incidence of vascular invasion and pulmonary colonization. Ectopic expression of miR-629-5p in A549 cells also increased their invasive capability. Then we identified that miR-629-5p promotes LUAD invasion in a mode of dual regulation via tumor cells invasion and endothelial cells permeability, respectively. In tumor cells, miR-629-5p enhanced motility and invasiveness of tumor cells by directly targeting PPWD1 (a cyclophilin), which clinically related to tumor invasion in LUAD specimens. Restoring PPWD1 protein significantly attenuated the invasion-promoting effects of miR-629-5p. Besides, exosomal-miR-629-5p secreted from tumor cells could be transferred to endothelial cells and increased endothelial monolayers permeability by suppressing CELSR1 (a nonclassic-type cadherin), which had a low level in the endothelial cells of invasive LUAD specimens. Activating the expression of CELSR1 in endothelial cells markedly blocked the effect of miR-629-5p. Our study suggests the dual roles of miR-629-5p in tumor cells and endothelial cells for LUAD invasion, implying a therapeutic option to targeting miR-629-5p using the "one stone, two birds" strategy in LUAD. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2bac28b136404a7c86681a178cd9da9cTest https://doi.org/10.1038/s41388-020-1228-1Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....2bac28b136404a7c86681a178cd9da9c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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