期刊
CELLS
卷 11, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/cells11172673
关键词
extracellular vesicle; hepatocellular carcinoma; miRNA; liquid biopsy; Sorafenib
类别
资金
- Instituto de Salud Carlos III (ISCiii) [PI16/00090, PI19/01266]
- Consejeria de Igualdad, Salud y Politicas Sociales [PI-0198-2016]
- Ministerio de Educacion, Cultura y Deporte [FPU17/00026]
- GEIVEX Mobility Fellowships 2020
- FPU estancias breves 2019 [EST19/01091]
- European Development Regional Fund A way to achieve Europe ERDF
- Instituto de Salud Carlos III [PI15/00145, PI18/0358, PI18/00768]
- AECC [PI044031]
- ISCIII
The study reveals that Sorafenib regulates a specific miRNA signature, where miR-200c-3p, miR-222-5p, and miR-512-3p have prognostic value and contribute to treatment response.
Background: Sorafenib constitutes a suitable treatment alternative for patients with advanced hepatocellular carcinoma (HCC) in whom atezolizumab + bevacizumab therapy is contraindicated. The aim of the study was the identification of a miRNA signature in liquid biopsy related to sorafenib response. Methods: miRNAs were profiled in hepatoblastoma HepG2 cells and tested in animal models, extracellular vesicles (EVs), and plasma from HCC patients. Results: Sorafenib altered the expression of 11 miRNAs in HepG2 cells. miR-200c-3p and miR-27a-3p exerted an anti-tumoral activity by decreasing cell migration and invasion, whereas miR-122-5p, miR-148b-3p, miR-194-5p, miR-222-5p, and miR-512-3p exerted pro-tumoral properties by increasing cell proliferation, migration, or invasion, or decreasing apoptosis. Sorafenib induced a change in EVs population with an increased number of larger EVs, and promoted an accumulation of miR-27a-3p, miR-122-5p, miR-148b-3p, miR-193b-3p, miR-194-5p, miR-200c-3p, and miR-375 into exosomes. In HCC patients, circulating miR-200c-3p baseline levels were associated with increased survival, whereas high levels of miR-222-5p and miR-512-3p after 1 month of sorafenib treatment were related to poor prognosis. The RNA sequencing revealed that miR-200c-3p was related to the regulation of cell growth and death, whereas miR-222-5p and miR-512-3p were related to metabolic control. Conclusions: The study showed that Sorafenib regulates a specific miRNA signature in which miR-200c-3p, miR-222-5p, and miR-512-3p bear prognostic value and contribute to treatment response.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据