SIRT7 promotes lung cancer progression by destabilizing the tumor suppressor ARF

Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD)-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain...

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Detalles Bibliográficos
Autores: Kumari, Poonam, Tarighi, Shahriar|||0000-0003-3807-9212, Fuchshuber, Eva, Li, Luhan, Fernández-Duran, Irene|||0000-0003-1289-7276, Wang, Meilin, Ayoson, Joshua, Castelló-García, Jose Manuel, Gámez-García, Andrés, Espinosa-Alcantud, María Dolores|||0000-0002-1126-2458, Sreenivasan, Krishnamoorthy|||0000-0001-8771-5911, Guenther, Stefan, Olivella, Mireia|||0000-0002-6035-3399, Savai, Rajkumar|||0000-0003-1538-2091, Yue, Shijing, Vaquero, Alejandro|||0000-0002-8735-4156, Braun, Thomas|||0000-0002-6165-4804, Ianni, Alessandro|||0000-0001-7398-589X
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:311100
Acceso en línea:https://ddd.uab.cat/record/311100
https://dx.doi.org/urn:doi:10.1073/pnas.2409269121
Access Level:acceso abierto
Palabra clave:ARF
SIRT7
Sirtuins
Lung cancer
Nucleophosmin
Descripción
Sumario:Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD)-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain largely uncharacterized. We demonstrate that SIRT7 exerts oncogenic functions in lung cancer cells by destabilizing the tumor suppressor alternative reading frame (ARF). SIRT7 directly interacts with ARF and prevents binding of ARF to nucleophosmin, thereby promoting proteasomal-dependent degradation of ARF. We show that SIRT7-mediated degradation of ARF increases expression of protumorigenic genes and stimulates proliferation of non-small-cell lung cancer (NSCLC) cells both in vitro and in vivo in a mouse xenograft model. Bioinformatics analysis of transcriptome data from human lung adenocarcinomas revealed a correlation between SIRT7 expression and increased activity of genes normally repressed by ARF. We propose that disruption of SIRT7-ARF signaling stabilizes ARF and thus attenuates cancer cell proliferation, offering a strategy to mitigate NSCLC progression.

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