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

Nat Struct Mol Biol. 2016 Jun;23(6):522-30. doi: 10.1038/nsmb.3211. Epub 2016 Apr 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast / metabolism
  • Breast / pathology
  • Cell Line, Tumor
  • DNA Breaks, Double-Stranded*
  • DNA End-Joining Repair*
  • Epidermal Growth Factor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • 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
  • Up-Regulation


  • LINP1 non-coding RNA, human
  • RNA, Long Noncoding
  • Tumor Suppressor Protein p53
  • Epidermal Growth Factor