Article

MiR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response

Stress and Cancer Laboratory, Institut Curie, Paris, France.
Nature medicine (Impact Factor: 28.05). 11/2011; 17(12):1627-35. DOI: 10.1038/nm.2512
Source: PubMed

ABSTRACT 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 p38α 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.

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Available from: Fatima Mechta-Grigoriou, Aug 31, 2015
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    • "Evidence is rapidly emerging for the role of miRNAs in gene regulation, demonstrating that miRNAs influence a diverse range of biological functions including cell differentiation and proliferation during normal development , but of higher relevance here is their role in pathological responses such as oxidative stress and inflammation (e.g. Lu et al. 2005; Mateescu et al. 2011). Exposure to environmental stresses (e.g. "
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    ABSTRACT: 1.To estimate the impact of urbanisation on wild animals, it is important to know how different species, populations and/or individuals deal with and respond to environmental stress. Are more urbanised species adapted to their environment; or do individuals acclimatize over the course of their life? Alternatively, do they simply cope at the expense of other functions? These are three key processes that I will address using two important physiological responses as case traits, namely oxidative stress and inflammation, - which are known to be under genetic control as well as showing great plasticity.2.Oxidative stress is a state of more reactive oxidants than antioxidants, which may cause tissue damage linked to disease and senescence. Inflammation, on the other hand, is the response of vascular tissues to harmful stimuli. However, under progressive stimuli inflammation may also cause tissue destruction and pathology.3.Although patterns and strengths of effects are not always clear cut, the often interconnected oxidative stress and inflammation have the potential to be severely affected by urban stressors, thereby mechanistically link ecology to fitness. Here I discuss five major urban stressors: chemical-, noise- and artificial night light pollution, disease and diet, and how their individual and combinatory effects may affect these two physiological responses.4.To start to disentangle whether physiological responses are a question of evolving, acclimatizing or coping with the urban environment, population genetics along with regulatory mechanisms of gene expression will shed light on the “costs” of urban life, and help to understand why some species or genotypes thrive, while others are absent, in urban areas. Single gene polymorphism (SNP) has been successful for explaining local adaptation and tolerance towards acute toxic substances. However, for multiple stressors acting in concert, at low chronic exposure, investigations of epigenetic mechanisms regulating gene expression may be more illuminating.5.Here I review the pathways by which genetic and epigenetic mechanisms can affect oxidative stress and inflammatory responses in urban environments, thereby affecting overall fitness. By doing so, I identify the major outstanding gaps of knowledge in the interfaces between ecology, toxicology, evolutionary and molecular biology to inform future studies of urban wildlife.This article is protected by copyright. All rights reserved.
    Functional Ecology 05/2015; 29(7). DOI:10.1111/1365-2435.12477 · 4.86 Impact Factor
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    • "The asterisk (*) in (B) indicates a statistically significant (P , 0.05) difference between the groups compared. a recent study, it was shown that miR-141 and miR-200a affect ovarian tumorigenesis by controlling the oxidative stress response (Mateescu et al., 2011). Furthermore, there were several miRs that were downregulated (varied from 1.5-to 2.5- fold) post-DES exposure. "
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    Molecular pharmacology 03/2015; 87(5). DOI:10.1124/mol.114.096743 · 4.12 Impact Factor
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    • "These data show that the chicken miR200 family is upregulated in ovarian tumors and that flaxseed was able to significantly inhibit the up-regulation of all three members in ovarian cancer by 55 to 80%. It has recently been shown that miR200 family members can be induced in ovarian cancer cells after exposure to oxidative stress [40]. Flaxseed acts as an antioxidant, particularly through the action of the lignan seicoisolariceresinol diglucoside, and its metabolites enterodiol and enterolactone [41, 42]. "
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