miR-139-5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of DNA repair and ROS defense.
Radiotherapy (RT) 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 (BC) via its regulation of genes involved in m...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Association for Cancer Research
2017
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| _version_ | 1826288700487630848 |
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| author | Pajic, M Froio, D Daly, S Doculara, L Millar, E Graham, PH Drury, A Steinmann, A de Bock, CE Boulghourjian, A Zaratzian, A Carroll, S Toohey, J O'Toole, SA Harris, AL Buffa, FM Gee, HE Hollway, GE Molloy, TJ |
| author_facet | Pajic, M Froio, D Daly, S Doculara, L Millar, E Graham, PH Drury, A Steinmann, A de Bock, CE Boulghourjian, A Zaratzian, A Carroll, S Toohey, J O'Toole, SA Harris, AL Buffa, FM Gee, HE Hollway, GE Molloy, TJ |
| author_sort | Pajic, M |
| collection | OXFORD |
| description | Radiotherapy (RT) 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 (BC) 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, specifically in RT-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant BC xenografts highly amenable to sensitization by co-treatment with a miR-139-5p mimetic. |
| first_indexed | 2024-03-07T02:17:39Z |
| format | Journal article |
| id | oxford-uuid:a2d1fc6e-f677-45e5-9e0d-38299cff1480 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:17:39Z |
| publishDate | 2017 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | oxford-uuid:a2d1fc6e-f677-45e5-9e0d-38299cff14802022-03-27T02:22:40ZmiR-139-5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of DNA repair and ROS defense.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a2d1fc6e-f677-45e5-9e0d-38299cff1480EnglishSymplectic Elements at OxfordAmerican Association for Cancer Research2017Pajic, MFroio, DDaly, SDoculara, LMillar, EGraham, PHDrury, ASteinmann, Ade Bock, CEBoulghourjian, AZaratzian, ACarroll, SToohey, JO'Toole, SAHarris, ALBuffa, FMGee, HEHollway, GEMolloy, TJRadiotherapy (RT) 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 (BC) 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, specifically in RT-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant BC xenografts highly amenable to sensitization by co-treatment with a miR-139-5p mimetic. |
| spellingShingle | Pajic, M Froio, D Daly, S Doculara, L Millar, E Graham, PH Drury, A Steinmann, A de Bock, CE Boulghourjian, A Zaratzian, A Carroll, S Toohey, J O'Toole, SA Harris, AL Buffa, FM Gee, HE Hollway, GE Molloy, TJ miR-139-5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of DNA repair and ROS defense. |
| title | miR-139-5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of DNA repair and ROS defense. |
| title_full | miR-139-5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of DNA repair and ROS defense. |
| title_fullStr | miR-139-5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of DNA repair and ROS defense. |
| title_full_unstemmed | miR-139-5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of DNA repair and ROS defense. |
| title_short | miR-139-5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of DNA repair and ROS defense. |
| title_sort | mir 139 5p modulates radiotherapy resistance in breast cancer by repressing multiple gene networks of dna repair and ros defense |
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