The Long Non-coding RNA Lnc-RAINY Regulates Genes Involved in Radiation Susceptibility Through DNA:DNA:RNA triplex-forming Interactions and has Tumor Therapeutic Potential in Non-small Cell Lung Cancers [RNA-seq]

Lung Cancer is the leading cause of cancer related deaths worldwide. Unfortunately, radiation resistance is a major problem facing lung cancer patients. Recently, we identified a group of long non-coding RNAs (lncRNAs) known as linc-SPRY3 RNAs, expressed from the Y-chromosome, that play a role in radiation sensitivity by decreasing tumor burden in vitro and in vivo after radiation. In this study, we found that the linc-SPRY3 RNAs are one large lncRNA that we named Radiation Induced Y-chromosome linked long non-coding RNA (lnc-RAINY). Through ATAC-Seq and Immunoprecipitation experiments, we show that lnc-RAINY interacts with DNA in a triple helix to change chromatin opening and gene expression. We also identified that lnc-RAINY regulates CDC6 and CDC25A expression affecting the induction of senescence, inhibition in cell migration, and cell cycle regulation. Furthermore, the administration of nanoparticle encapsulated lnc-RAINY into a lung cancer patient-derived xenograft model dramatically reduces tumor progression demonstrating its therapeutic potential. Overall design: To understand the impact of lnc-RAINY on gene expression, we used 3 siRNAs against lnc-RAINY to identify differential gene expression after radiation, with or without the presence of lnc-RAINY.