@misc{10481/77030,
year = {2022},
month = {8},
url = {https://hdl.handle.net/10481/77030},
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.},
organization = {Instituto de Salud Carlos III},
organization = {European Commission	PI16/00090	
PI19/01266},
organization = {Consejeria de Igualdad, Salud y Politicas Sociales	PI-0198-2016},
organization = {Spanish Government	FPU17/00026},
organization = {GEIVEX Mobility Fellowships 2020},
organization = {German Research Foundation (DFG)},
organization = {National Health and Medical Research Council (NHMRC) of Australia	EST19/01091},
organization = {European Commission},
organization = {Instituto de Salud Carlos III},
organization = {European Commission	PI15/00145	
PI18/0358	
PI18/00768},
organization = {AECC	PI044031},
organization = {Instituto de Salud Carlos III},
publisher = {MDPI},
keywords = {Extracellular vesicle},
keywords = {Hepatocellular carcinoma},
keywords = {miRNA},
keywords = {Liquid biopsy},
keywords = {Sorafenib},
title = {miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma},
doi = {10.3390/cells11172673},
author = {De La Cruz Ojeda, Patricia and Praena Fernández, Juan Manuel},
}