Cruz Ojeda, Patricia de laSchmid, TobiasBoix, LoretoMoreno, ManuelaSapena, VíctorPraena Fernandez, Juan ManuelGómez Bravo, Miguel ÁngelMuntané Relat, Jordi2023-04-212023-04-212022-08-28Cruz Ojeda, P.d.l., Schmid, T., Boix, L., Moreno, M., Sapena, V., Praena Fernandez, J.M.,...,Muntané Relat, J. (2022). miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma. Cells, 11 (17), 2673. https://doi.org/doi.org/10.3390/cells11172673.2073-4409https://hdl.handle.net/11441/144757Background: 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.application/pdf24 p.engAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/extracellular vesiclehepatocellular carcinomamiRNAliquid biopsySorafenibinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/doi.org/10.3390/cells11172673