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

• Published in: Nature structural & molecular biology Vol. 23; no. 6; pp. 522 - 530
• Main Authors: Zhang, Youyou, He, Qun, Hu, Zhongyi, Feng, Yi, Fan, Lingling, Tang, Zhaoqing, Yuan, Jiao, Shan, Weiwei, Li, Chunsheng, Hu, Xiaowen, Tanyi, Janos L, Fan, Yi, Huang, Qihong, Montone, Kathleen, Dang, Chi V, Zhang, Lin
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2016; Nature Publishing Group
• Subjects: 631/208; 692/699/67; Biochemistry; Biological Microscopy; Breast - metabolism; Breast - pathology; Breast cancer; Care and treatment; Cell Line, Tumor; Cellular signal transduction; Deoxyribonucleic acid; Development and progression; DNA; DNA Breaks, Double-Stranded; DNA damage; DNA End-Joining Repair; DNA repair; Epidermal Growth Factor - metabolism; Female; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetic screening; Health aspects; Humans; Life Sciences; Membrane Biology; Properties; Protein expression; Protein Structure; Protein-protein interactions; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Tumor Suppressor Protein p53 - metabolism; Tumorigenesis; Up-Regulation
• ISSN: 1545-9993; 1545-9985; 1545-9985
• DOI: 10.1038/nsmb.3211

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.