Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion

Cancer is characterized by genomic instability leading to deletion or amplification of oncogenes or tumor suppressors. However, most of the altered regions are devoid of known cancer drivers. Here, we identify lncRNAs frequently lost or amplified in cancer. Among them, we found amplified lncRNA asso...

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Detalles Bibliográficos
Autores: Athie, Alejandro, Marchese, Francesco P., González, Jovanna, Lozano, Teresa, Raimondi, Ivan, Juvvuna, Prasanna Kumar, Abad, Amaya, Marín-Béjar, Oskar, Serizay, Jacques, Martínez, Dannys, Ajona, Daniel, Pajares Villandiego, María Josefa, Sandoval, Juan, Montuenga, Luis M., Kanduri, Chandrasekhar, Lasarte, Juan José, Huarte, Maite
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/53107
Acceso en línea:https://hdl.handle.net/2454/53107
Access Level:acceso abierto
Palabra clave:Cancer
RNA biology
lncRNA
ALAL-1
Descripción
Sumario:Cancer is characterized by genomic instability leading to deletion or amplification of oncogenes or tumor suppressors. However, most of the altered regions are devoid of known cancer drivers. Here, we identify lncRNAs frequently lost or amplified in cancer. Among them, we found amplified lncRNA associated with lung cancer-1 (ALAL-1) as frequently amplified in lung adenocarcinomas. ALAL-1 is also overexpressed in additional tumor types, such as lung squamous carcinoma. The RNA product of ALAL-1 is able to promote the proliferation and tumorigenicity of lung cancer cells. ALAL-1 is a TNFα− and NF-κB–induced cytoplasmic lncRNA that specifically interacts with SART3, regulating the subcellular localization of the protein deubiquitinase USP4 and, in turn, its function in the cell. Interestingly, ALAL-1 expression inversely correlates with the immune infiltration of lung squamous tumors, while tumors with ALAL-1 amplification show lower infiltration of several types of immune cells. We have thus unveiled a pro-oncogenic lncRNA that mediates cancer immune evasion, pointing to a new target for immune potentiation.

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