Detalle Publicación

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

Autores: Athie, A. ; Marchese, Francesco Paolo; González Rojas, Sandra Jovanna; Lozano Moreda, Teresa; Raimondi, I. ; Juvvuna, P. K. ; Abad, A. ; Marin-Bejar, O.; Serizay, J. ; Martinez, D.; Ajona Martínez-Polo, Daniel; Pajares, M. J.; Sandoval, J.; Montuenga Badía, Luis; Kanduri, C.; Lasarte Sagastibelza, Juan José; Huarte Martínez, Maite (Autor de correspondencia)
Título de la revista: JOURNAL OF CELL BIOLOGY
ISSN: 0021-9525
Volumen: 219
Número: 9
Fecha de publicación: 2020
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 IncRNA 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 TNF alpha- and NF-kappa B-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.