Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative 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.
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Youyou
Y
Zhang
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Qun
Q
He
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Zhongyi
Z
Hu
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Yi
Y
Feng
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Lingling
L
Fan
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Zhaoqing
Z
Tang
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jiao
J
Yuan
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Weiwei
W
Shan
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Chunsheng
C
Li
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Xiaowen
X
Hu
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Janos L
JL
Tanyi
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Yi
Y
Fan
Wistar Institute, Philadelphia, Pennsylvania, USA.
Qihong
Q
Huang
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kathleen
K
Montone
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Chi V
CV
Dang
Center for Research on Reproduction &Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Lin
L
Zhang
D001940:Breast / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
C000619001:LINP1 non-coding RNA, human; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; D004815:Epidermal Growth Factor