RT Journal Article
T1 miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma.
A1 de la Cruz-Ojeda, Patricia
A1 Schmid, Tobias
A1 Boix, Loreto
A1 Moreno, Manuela
A1 Sapena, Víctor
A1 Praena-Fernández, Juan M
A1 Castell, Francisco J
A1 Falcón-Pérez, Juan Manuel
A1 Reig, María
A1 Brüne, Bernhard
A1 Gómez-Bravo, Miguel A
A1 Giráldez, Álvaro
A1 Bruix, Jordi
A1 Ferrer, María T
A1 Muntané, Jordi
K1 Sorafenib
K1 extracellular vesicle
K1 hepatocellular carcinoma
K1 liquid biopsy
K1 miRNA
AB 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. miRNAs were profiled in hepatoblastoma HepG2 cells and tested in animal models, extracellular vesicles (EVs), and plasma from HCC patients. 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. 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.
YR 2022
FD 2022-08-28
LK http://hdl.handle.net/10668/20935
UL http://hdl.handle.net/10668/20935
LA en
DS RISalud
RD Apr 8, 2025