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Verfasst von:Dell'Anno, Irene [VerfasserIn]   i
 Catalano, Calogerina [VerfasserIn]   i
Titel:EIF4G1 and RAN as possible drivers for malignant pleural mesothelioma
Verf.angabe:Irene Dell’Anno, Marcella Barbarino, Elisa Barone, Antonio Giordano, Luca Luzzi, Maria Bottaro, Loredana Migliore, Silvia Agostini, Alessandra Melani, Ombretta Melaiu, Calogerina Catalano, Monica Cipollini, Roberto Silvestri, Alda Corrado, Federica Gemignani and Stefano Landi
E-Jahr:2020
Jahr:9 July 2020
Umfang:18 S.
Fussnoten:Im Titel ist "EIF4G1" und "RAN" in kursiver Schrift dargestellt ; Gesehen am 23.10.2020
Titel Quelle:Enthalten in: International journal of molecular sciences
Ort Quelle:Basel : Molecular Diversity Preservation International, 2000
Jahr Quelle:2020
Band/Heft Quelle:21(2020,14) Artikel-Nummer 4856, 18 Seiten
ISSN Quelle:1422-0067
 1661-6596
Abstract:For malignant pleural mesothelioma (MPM) novel therapeutic strategies are urgently needed. In a previous study, we identified 51 putative cancer genes over-expressed in MPM tissues and cell lines. Here, we deepened the study on nine of them (ASS1, EIF4G1, GALNT7, GLUT1, IGF2BP3 (IMP3), ITGA4, RAN, SOD1, and THBS2) to ascertain whether they are truly mesothelial cancer driver genes (CDGs) or genes overexpressed in an adaptive response to the tumoral progression (“passenger genes”). Through a fast siRNA-based screening, we evaluated the consequences of gene depletion on migration, proliferation, colony formation capabilities, and caspase activities of four MPM (Mero-14, Mero-25, IST-Mes2, and NCI-H28) and one SV40-immortalized mesothelial cell line (MeT-5A) as a non-malignant model. The depletion of EIF4G1 and RAN significantly reduced cell proliferation and colony formation and increased caspase activity. In particular, the findings for RAN resemble those observed for other types of cancer. Thus, we evaluated the in vitro effects of importazole (IPZ), a small molecule inhibitor of the interaction between RAN and importin-β. We showed that IPZ could have effects similar to those observed following RAN gene silencing. We also found that primary cell lines from one out of three MPM patients were sensitive to IPZ. As EIF4G1 and RAN deserve further investigation with additional in vitro and in vivo studies, they emerged as promising CDGs, suggesting that their upregulation could play a role in mesothelial tumorigenesis and aggressiveness. Furthermore, present data propose the molecular pathways dependent on RAN as a putative pharmacological target for MPM patients in the view of a future personalized medicine.
DOI:doi:10.3390/ijms21144856
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.3390/ijms21144856
 Volltext: https://www.mdpi.com/1422-0067/21/14/4856
 DOI: https://doi.org/10.3390/ijms21144856
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1736475576
Verknüpfungen:→ Zeitschrift

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