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miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma
dc.contributor.author | De La Cruz Ojeda, Patricia | |
dc.contributor.author | Praena Fernández, Juan Manuel | |
dc.date.accessioned | 2022-09-28T07:39:23Z | |
dc.date.available | 2022-09-28T07:39:23Z | |
dc.date.issued | 2022-08-28 | |
dc.identifier.citation | de la Cruz-Ojeda, P... [et al.]. miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma. Cells 2022, 11, 2673. [https://doi.org/10.3390/cells11172673] | es_ES |
dc.identifier.uri | https://hdl.handle.net/10481/77030 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | Instituto de Salud Carlos III | es_ES |
dc.description.sponsorship | European Commission PI16/00090 PI19/01266 | es_ES |
dc.description.sponsorship | Consejeria de Igualdad, Salud y Politicas Sociales PI-0198-2016 | es_ES |
dc.description.sponsorship | Spanish Government FPU17/00026 | es_ES |
dc.description.sponsorship | GEIVEX Mobility Fellowships 2020 | es_ES |
dc.description.sponsorship | German Research Foundation (DFG) | es_ES |
dc.description.sponsorship | National Health and Medical Research Council (NHMRC) of Australia EST19/01091 | es_ES |
dc.description.sponsorship | European Commission | es_ES |
dc.description.sponsorship | Instituto de Salud Carlos III | es_ES |
dc.description.sponsorship | European Commission PI15/00145 PI18/0358 PI18/00768 | es_ES |
dc.description.sponsorship | AECC PI044031 | es_ES |
dc.description.sponsorship | Instituto de Salud Carlos III | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Extracellular vesicle | es_ES |
dc.subject | Hepatocellular carcinoma | es_ES |
dc.subject | miRNA | es_ES |
dc.subject | Liquid biopsy | es_ES |
dc.subject | Sorafenib | es_ES |
dc.title | miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma | es_ES |
dc.type | journal article | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.identifier.doi | 10.3390/cells11172673 | |
dc.type.hasVersion | VoR | es_ES |