GSE134141
The analysis of copy number alterations from a lncRNA perspective reveals 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 independently of protein-coding genes. 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 through epigenetic mechanisms. The RNA product of ALAL-1 is able to promote the proliferation and tumorigenicity of lung cancer cells. ALAL-1 is a TNF and NF-?B-induced cytoplasmic lncRNA that specifically interacts with SART3 co-regulating TNF, p53, NF-?B, TGF-ß1 and IL8 pathways. Interestingly, ALAL-1 expression inversely correlates with the immune infiltration of lung squamous tumors, and 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. Overall design: Analysis of the transcriptomic changes following ALAL-1 or SART3 knockdown by RNAi in HCC95 cells treated or not with TNF. Each experimental condition was performed in triplicates.