Lnc-RAINY regulates genes involved in radiation susceptibility through DNA:DNA:RNA triplex-forming interactions and has tumor therapeutic potential in lung cancers.
作者信息
Westemeier-Rice Emily S, Winters Michael T, Rawson Travis W, Patel Kiran J, McHugh Olivia, Ward Sierra, McLaughlin Sarah, Stewart Amanda, Misra Bishal, Dziadowicz Sebastian, Yi Weijun, Bobbala Sharan, Hu Gangqing, Martinez Ivan
机构信息
West Virginia University Cancer Institute, West Virginia University, West Virginia, United States.
Department of Microbiology, Immunology and Cell Biology, West Virginia University, West Virginia, United States.
出版信息
Noncoding RNA Res. 2024 Dec 18;12:152-166. doi: 10.1016/j.ncrna.2024.12.004. eCollection 2025 Jun.
Lung cancer is the leading cause of cancer related deaths worldwide. Unfortunately, radiation resistance remains a major problem facing lung cancer patients. Recently, we identified a group of long non-coding RNAs (lncRNAs) known as linc-SPRY3 RNAs, expressed on the Y-chromosome, which play a role in radiation sensitivity by decreasing tumor burden and after radiation. In this study, we found that the linc-SPRY3 RNAs are one large lncRNA that we named diation duced -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 induce chromatin remodeling and gene expression. We also identified that lnc-RAINY regulates CDC6 and CDC25A expression affecting senescence induction, cell migration patterns, and cell cycle regulation. Furthermore, the administration of Lnc-RAINY encapsulated in FDA-approved nanoparticles into a lung cancer patient-derived xenograft model dramatically reduces tumor progression demonstrating therapeutic potential.