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

Youyou Zhang, Qun He, Zhongyi Hu, Y. Feng, Lingling Fan, Zhaoqing Tang, Jiao Yuan, Weiwei Shan, Chunsheng Li, Xiaowen Hu, Janos L. Tanyi, Y. Fan, Qihong Huang, Kathleen Montone, Chi V. Dang, Lin Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalNature structural & molecular biology
DOIs
StateAccepted/In press - Apr 25 2016
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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