miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma
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....
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/17/2673 |
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| author | Patricia de la Cruz-Ojeda Tobias Schmid Loreto Boix Manuela Moreno Víctor Sapena Juan M. Praena-Fernández Francisco J. Castell Juan Manuel Falcón-Pérez María Reig Bernhard Brüne Miguel A. Gómez-Bravo Álvaro Giráldez Jordi Bruix María T. Ferrer Jordi Muntané |
| author_facet | Patricia de la Cruz-Ojeda Tobias Schmid Loreto Boix Manuela Moreno Víctor Sapena Juan M. Praena-Fernández Francisco J. Castell Juan Manuel Falcón-Pérez María Reig Bernhard Brüne Miguel A. Gómez-Bravo Álvaro Giráldez Jordi Bruix María T. Ferrer Jordi Muntané |
| author_sort | Patricia de la Cruz-Ojeda |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:57:13Z |
| format | Article |
| id | doaj.art-cc87b80748a249959a5277e17b1b319e |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:57:13Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cc87b80748a249959a5277e17b1b319e2023-11-23T12:55:01ZengMDPI AGCells2073-44092022-08-011117267310.3390/cells11172673miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular CarcinomaPatricia de la Cruz-Ojeda0Tobias Schmid1Loreto Boix2Manuela Moreno3Víctor Sapena4Juan M. Praena-Fernández5Francisco J. Castell6Juan Manuel Falcón-Pérez7María Reig8Bernhard Brüne9Miguel A. Gómez-Bravo10Álvaro Giráldez11Jordi Bruix12María T. Ferrer13Jordi Muntané14Institute of Biomedicine of Seville (IBiS), Hospital University “Virgen del Rocío”/CSIC/University of Seville, 41013 Seville, SpainInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60528 Frankfurt, GermanyNetworked Biomedical Research Center Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, SpainDepartment of General Surgery, Hospital University “Virgen del Rocío”/CSIC/University of Seville/IBIS, 41013 Seville, SpainBCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBEREHD, 08036 Barcelona, SpainDepartment of Statistics and Operations Research, University of Granada, 18011 Granada, SpainDepartment of Radiology, Hospital University “Virgen del Rocío”/CSIC/University of Seville/IBIS, 41013 Seville, SpainNetworked Biomedical Research Center Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, SpainNetworked Biomedical Research Center Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, SpainInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60528 Frankfurt, GermanyDepartment of General Surgery, Hospital University “Virgen del Rocío”/CSIC/University of Seville/IBIS, 41013 Seville, SpainUnit for the Clinical Management of Digestive Diseases, Hospital University “Virgen del Rocío”/CSIC/University of Seville/IBIS, 41013 Seville, SpainNetworked Biomedical Research Center Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, SpainUnit for the Clinical Management of Digestive Diseases, Hospital University “Virgen del Rocío”/CSIC/University of Seville/IBIS, 41013 Seville, SpainInstitute of Biomedicine of Seville (IBiS), Hospital University “Virgen del Rocío”/CSIC/University of Seville, 41013 Seville, SpainBackground: 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.https://www.mdpi.com/2073-4409/11/17/2673extracellular vesiclehepatocellular carcinomamiRNAliquid biopsySorafenib |
| spellingShingle | Patricia de la Cruz-Ojeda Tobias Schmid Loreto Boix Manuela Moreno Víctor Sapena Juan M. Praena-Fernández Francisco J. Castell Juan Manuel Falcón-Pérez María Reig Bernhard Brüne Miguel A. Gómez-Bravo Álvaro Giráldez Jordi Bruix María T. Ferrer Jordi Muntané miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma Cells extracellular vesicle hepatocellular carcinoma miRNA liquid biopsy Sorafenib |
| title | miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma |
| title_full | miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma |
| title_fullStr | miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma |
| title_full_unstemmed | miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma |
| title_short | miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma |
| title_sort | mir 200c 3p mir 222 5p and mir 512 3p constitute a biomarker signature of sorafenib effectiveness in advanced hepatocellular carcinoma |
| topic | extracellular vesicle hepatocellular carcinoma miRNA liquid biopsy Sorafenib |
| url | https://www.mdpi.com/2073-4409/11/17/2673 |
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