Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion.
A549 Cells
Adenocarcinoma of Lung
/ genetics
Antigens, Neoplasm
/ genetics
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
DNA Copy Number Variations
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Immune Evasion
/ genetics
Lung Neoplasms
/ genetics
NF-kappa B
/ genetics
Oncogenes
/ genetics
RNA, Long Noncoding
/ genetics
Ubiquitin-Specific Proteases
/ genetics
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
07 09 2020
07 09 2020
Historique:
received:
08
08
2019
revised:
12
12
2019
accepted:
05
06
2020
entrez:
29
8
2020
pubmed:
29
8
2020
medline:
23
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32858747
pii: 152052
doi: 10.1083/jcb.201908078
pmc: PMC7480115
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
NF-kappa B
0
RNA, Long Noncoding
0
Ubiquitin-Specific Proteases
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
ID : 281877
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Athie et al.
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