Comprehensive analysis of long non-coding RNAs expression associated with hypoxia and prognosis in non-small cell lung cancer

Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. It is therefore essential to identify new prognostic markers and new therapeutic targets. We are interested in gene regulation related to hypoxia, a factor associated with relapse of lung adenocarcinomas (LUAD). While long non-coding RNAs (lncRNA) are increasingly recognized as major gene expression regulators through various molecular mechanisms, their roles in cancer development and hypoxic response are still largely unexplored. Combining profiling studies on A549 LUAD cell line cultured in normoxic or hypoxic conditions and on early stages LUAD biopsies, we identified a signature of lncRNAs that are regulated by hypoxia in vitro and correlated to i) the hypoxic status of tumors and/or ii) the overall survival of patients. We focused on a candidate, LINC01116, and confirmed this dysregulation on public datasets from larger LUAD and LUSC (Lung Squamous Cell Carcinomas) cohorts of "The Cancer Genome Atlas". We showed that LINC01116 is a short cytosolic transcript composed of 3 exons. Using RNA FISH imaging, RNA interference knock-down and transcriptome analyses, we suggest its potential implication in cellular morphology and cell-to-cell contact. In addition, we found a correlation between LINC01116 expression and an alpha catenin gene network involved in cell-to-cell signaling.