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

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

Author information

1
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
2
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
3
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
4
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5
Wistar Institute, Philadelphia, Pennsylvania, USA.
6
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
7
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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.

PMID:
27111890
PMCID:
PMC4927085
DOI:
10.1038/nsmb.3211
[Indexed for MEDLINE]
Free PMC Article

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