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 t...

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Published inNature 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
Long noncoding RNAs (IncRNAs) 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.
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.
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.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.
Audience Academic
Author Feng, Yi
Fan, Lingling
Yuan, Jiao
Montone, Kathleen
Zhang, Youyou
Hu, Xiaowen
Fan, Yi
He, Qun
Li, Chunsheng
Huang, Qihong
Zhang, Lin
Hu, Zhongyi
Dang, Chi V
Tanyi, Janos L
Shan, Weiwei
Tang, Zhaoqing
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  organization: Center for Research on Reproduction & Women's Health, University of Pennsylvania
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  organization: Center for Research on Reproduction & Women's Health, University of Pennsylvania, Abramson Family Cancer Research Institute, University of Pennsylvania
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  organization: Center for Research on Reproduction & Women's Health, University of Pennsylvania
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  organization: Center for Research on Reproduction & Women's Health, University of Pennsylvania
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– sequence: 10
  givenname: Xiaowen
  surname: Hu
  fullname: Hu, Xiaowen
  organization: Center for Research on Reproduction & Women's Health, University of Pennsylvania, Department of Obstetrics and Gynecology, University of Pennsylvania
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  organization: Wistar Institute
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  organization: Department of Pathology and Laboratory Medicine, University of Pennsylvania
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  email: dangvchi@exchange.upenn.edu
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  surname: Zhang
  fullname: Zhang, Lin
  email: linzhang@mail.med.upenn.edu
  organization: Center for Research on Reproduction & Women's Health, University of Pennsylvania, Department of Obstetrics and Gynecology, University of Pennsylvania, Abramson Cancer Center, University of Pennsylvania
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27111890$$D View this record in MEDLINE/PubMed
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Snippet New data reveal that LINP1, a lncRNA overexpressed in triple-negative breast cancer, interacts with the Ku70–Ku80 complex and DNA-PKcs, thereby promoting...
Long noncoding RNAs (lncRNAs) play critical roles during tumorigenesis by functioning as scaffolds that regulate protein-protein, protein-DNA or protein-RNA...
Long noncoding RNAs (IncRNAs) play critical roles during tumorigenesis by functioning as scaffolds that regulate protein-protein, protein-DNA or protein-RNA...
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SubjectTerms 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
Title Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer
URI https://link.springer.com/article/10.1038/nsmb.3211
https://www.ncbi.nlm.nih.gov/pubmed/27111890
https://www.proquest.com/docview/1794510386
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https://www.proquest.com/docview/1808714403
Volume 23
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