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: 27.36). 11/2011; 17(12):1627-35. DOI: 10.1038/nm.2512
Source: PubMed


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
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    • "These results suggested that miR-141 is the most likely candidate miRNA regulating SPAG9 expression in liver tumorigenesis. MiR-141 is negatively regulated in different types of cancers and is considered to be a tumor suppressor, e.g., ovarian cancer, breast cancer, or gastric cancer, by targeting a number of important genes such as p38α[28], Stat5a[29], TAZ[30], and others[31,32]. Moreover, several in vivo studies have shown that the overexpression of miR-141 could suppress tumor growth and metastasis in a tumor xenograft mice model[30,33]. "
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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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    • "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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