Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer

New data reveal that LINP1, a lncRNA overexpressed in triple-negative breast cancer, interacts with the Ku70–Ku80 complex and DNA-PKcs, thereby promoting NHEJ-mediated DNA double-strand-break repair. Long noncoding RNAs (lncRNAs) play critical roles during tumorigenesis by functioning as scaffolds that regulate protein-protein, protein-DNA or protein-RNA interactions. Using a clinically guided genetic screening approach, we identified lncRNA in nonhomologous end joining (NHEJ) pathway 1 (LINP1), which is overexpressed in human triple-negative breast cancer. We found that LINP1 enhances repair of DNA double-strand breaks by serving as a scaffold linking Ku80 and DNA-PKcs, thereby coordinating the NHEJ pathway. Importantly, blocking LINP1, which is regulated by p53 and epidermal growth factor receptor (EGFR) signaling, increases the sensitivity of the tumor-cell response to radiotherapy in breast cancer.