Long Noncoding RNA Protects Oral Squamous Cell Carcinoma Cells from Endoplasmic Reticulum Stress-Induced Apoptosis via Promoting MRE11-RAD50-NBS1 Complex Formation.

Recent studies have proven that long noncoding RNAs (lncRNAs) exhibit regulatory functions of both DNA damage response (DDR) and endoplasmic reticulum (ER) stress. Herein, ER stress-induced lncRNA transcriptomic changes are reported in human oral squamous cell carcinoma (OSCC) cells and a novel lncRNA ( nronic ranscript of tress) is identified as the most significantly upregulated lncRNA. It is shown that is a nucleus-located lncRNA including two transcript variants. lacks an independent promoter but shares the same promoter with . is transcriptionally regulated by , , , and DNA methylation. In human OSCC tissues, is significantly correlated with OSCC clinicopathological features and prognosis. Gain- and loss-of-function studies reveal that promotes OSCC proliferation and invasion via influencing the expression of growth factor receptors and the downstream pathways. Once ER stress is triggered, significantly attenuates ER stress-induced apoptosis both in vivo and in vitro. Mechanically, functions as RNA scaffold to promote MRE11-RAD50-NBS1 complex formation in the repair of ER stress-induced DNA damage. To sum up, this study presents a novel lncRNA, namely , which links ER stress and DDR together in OSCC.