Journal
NATURE MEDICINE
Volume 17, Issue 12, Pages 1627-U144Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2512
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Funding
- Institut National de la Sante et de la Recherche Medicale
- Institut Curie
- Ligue Nationale Contre le Cancer
- Institut National du Cancer
- Association pour la Recherche Contre le Cancer
- INSERM
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Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38 alpha and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38 alpha deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38 alpha and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials.
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