Analysis of Copy Number Alterations Reveals the LncRNA ALAL-1 As a Regulator of Lung Cancer Immune Evasion

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2020 Aug 29

PMID 32858747

Citations 23

Authors

Alejandro Athie

Francesco P Marchese

Jovanna Gonzalez

Teresa Lozano

Ivan Raimondi

Prasanna Kumar Juvvuna

Amaya Abad

Oskar Marin-Bejar

Jacques Serizay

Dannys Martinez

Daniel Ajona

Maria Jose Pajares

Juan Sandoval

Luis M Montuenga

Chandrasekhar Kanduri

Juan J Lasarte

Maite Huarte

Affiliations

Soon will be listed here.

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-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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