Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion
Abstract
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 (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
Cite
Athie A, Marchese FP, González J, Lozano T, Raimondi I, Juvvuna PK, et al. Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion. Journal of Cell Biology. 2020;219(9):e201908078. doi:10.1083/jcb.201908078
@article{athie_jcb_2020,
author = {Athie, Alejandro and Marchese, Francesco P. and González, Jovanna and Lozano, Teresa and Raimondi, Ivan and Juvvuna, Prasanna Kumar and Abad, Amaya and Marin-Bejar, Oskar and Serizay, Jacques and Martínez, Dannys and Ajona, Daniel and Pajares, Maria Jose and Sandoval, Juan and Montuenga, Luis M. and Kanduri, Chandrasekhar and Lasarte, Juan J. and Huarte, Maite},
title = {{Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion}},
journal = {Journal of Cell Biology},
year = {2020},
volume = {219},
number = {9},
pages = {e201908078},
doi = {10.1083/jcb.201908078},
url = {https://doi.org/10.1083/jcb.201908078}
}