miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response
A partir d'échantillons tumoraux prélevés sur des patientes traitées pour un carcinome ovarien à l'Institut Curie entre 1989 et 2005, cette étude identifie deux signatures, basées sur l'expression de micro-ARNs impliqués dans la régulation du stress oxydant, en association avec la réponse à une chimiothérapie
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
α and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38α 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 p38α 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.
Nature Medicine , résumé, 2010