期刊
CANCER RESEARCH
卷 78, 期 2, 页码 501-515出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-16-3105
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资金
- Cancer Institute New South Wales [11-CDF-3-25, 13/CDF/1-01]
- Philip Hemstritch Fellowship in Pancreatic Cancer
- National Foundation for Medical Research and Innovation
- National Breast Cancer Foundation
- Chris O'Brien Lifehouse
- CASS Foundation
- MRC [G0300648] Funding Source: UKRI
- Cancer Research UK [11359, 18974, 16466, 23969] Funding Source: researchfish
- Medical Research Council [G0300648] Funding Source: researchfish
- National Breast Cancer Foundation [PRAC-16-006] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10163] Funding Source: researchfish
Radiotherapy is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo, resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage, and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome in radiotherapy-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant breast cancer xenografts highly amenable to sensitization by cotreatment with a miR-139-5p mimetic. Significance: The microRNA described in this study offers a potentially useful predictive biomarker of radiosensitivity in solid tumors and a generally applicable druggable target for tumor radiosensitization. (C) 2017 AACR.
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