miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma
Metadatos
Mostrar el registro completo del ítemEditorial
MDPI
Materia
Extracellular vesicle Hepatocellular carcinoma miRNA Liquid biopsy Sorafenib
Fecha
2022-08-28Referencia bibliográfica
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]
Patrocinador
Instituto de Salud Carlos III; European Commission PI16/00090 PI19/01266; Consejeria de Igualdad, Salud y Politicas Sociales PI-0198-2016; Spanish Government FPU17/00026; GEIVEX Mobility Fellowships 2020; German Research Foundation (DFG); National Health and Medical Research Council (NHMRC) of Australia EST19/01091; European Commission; Instituto de Salud Carlos III; European Commission PI15/00145 PI18/0358 PI18/00768; AECC PI044031; Instituto de Salud Carlos IIIResumen
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.