MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib
In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studie...
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| Format: | Online |
| Language: | English |
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Impact Journals LLC
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058693/ |
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pubmed-50586932016-10-15 MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib Lassalle, Sandra Zangari, Joséphine Popa, Alexandra Ilie, Marius Hofman, Véronique Long, Elodie Patey, Martine Tissier, Frédérique Belléannée, Geneviève Trouette, Hélène Catargi, Bogdan Peyrottes, Isabelle Sadoul, Jean-Louis Bordone, Olivier Bonnetaud, Christelle Butori, Catherine Bozec, Alexandre Guevara, Nicolas Santini, José Hénaoui, Imène Sarah Lemaire, Géraldine Blanck, Olivier Vielh, Philippe Barbry, Pascal Mari, Bernard Brest, Patrick Hofman, Paul Research Paper In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib. Impact Journals LLC 2016-03-29 /pmc/articles/PMC5058693/ /pubmed/27036030 http://dx.doi.org/10.18632/oncotarget.8458 Text en Copyright: © 2016 Lassalle et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Lassalle, Sandra Zangari, Joséphine Popa, Alexandra Ilie, Marius Hofman, Véronique Long, Elodie Patey, Martine Tissier, Frédérique Belléannée, Geneviève Trouette, Hélène Catargi, Bogdan Peyrottes, Isabelle Sadoul, Jean-Louis Bordone, Olivier Bonnetaud, Christelle Butori, Catherine Bozec, Alexandre Guevara, Nicolas Santini, José Hénaoui, Imène Sarah Lemaire, Géraldine Blanck, Olivier Vielh, Philippe Barbry, Pascal Mari, Bernard Brest, Patrick Hofman, Paul |
| spellingShingle |
Lassalle, Sandra Zangari, Joséphine Popa, Alexandra Ilie, Marius Hofman, Véronique Long, Elodie Patey, Martine Tissier, Frédérique Belléannée, Geneviève Trouette, Hélène Catargi, Bogdan Peyrottes, Isabelle Sadoul, Jean-Louis Bordone, Olivier Bonnetaud, Christelle Butori, Catherine Bozec, Alexandre Guevara, Nicolas Santini, José Hénaoui, Imène Sarah Lemaire, Géraldine Blanck, Olivier Vielh, Philippe Barbry, Pascal Mari, Bernard Brest, Patrick Hofman, Paul MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib |
| author_facet |
Lassalle, Sandra Zangari, Joséphine Popa, Alexandra Ilie, Marius Hofman, Véronique Long, Elodie Patey, Martine Tissier, Frédérique Belléannée, Geneviève Trouette, Hélène Catargi, Bogdan Peyrottes, Isabelle Sadoul, Jean-Louis Bordone, Olivier Bonnetaud, Christelle Butori, Catherine Bozec, Alexandre Guevara, Nicolas Santini, José Hénaoui, Imène Sarah Lemaire, Géraldine Blanck, Olivier Vielh, Philippe Barbry, Pascal Mari, Bernard Brest, Patrick Hofman, Paul |
| author_sort |
Lassalle, Sandra |
| title |
MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib |
| title_short |
MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib |
| title_full |
MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib |
| title_fullStr |
MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib |
| title_full_unstemmed |
MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib |
| title_sort |
microrna-375/sec23a as biomarkers of the in vitro efficacy of vandetanib |
| description |
In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib. |
| publisher |
Impact Journals LLC |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058693/ |
| _version_ |
1613679931512848384 |