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PMID: 22101765 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature medicine ·Vol. 17 ·No. 12 ·2011-11-20 ·Pages 1627-35

Mateescu B, Batista L, Cardon M, Gruosso T, de Feraudy Y, Mariani O, Nicolas A, Meyniel JP, Cottu P, Sastre-Garau X, Mechta-Grigoriou F

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.

MeSH Terms
Adult Aged Aged, 80 and over Animals Carcinoma, Ovarian Epithelial Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic/genetics Down-Regulation Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Mice Mice, Nude MicroRNAs/genetics,metabolism Middle Aged Mitogen-Activated Protein Kinase 14/genetics,metabolism Neoplasms, Glandular and Epithelial/genetics,pathology Ovarian Neoplasms/genetics,pathology Oxidative Stress
Chemicals
MIRN141 microRNA, human MIRN200 microRNA, human MicroRNAs Mirn141 microRNA, mouse Mirn200 microRNA, mouse Mitogen-Activated Protein Kinase 14
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Mateescu Bogdan
Stress and Cancer Laboratory, Institut Curie, Paris, France.
Batista Luciana
Cardon Melissa
Gruosso Tina
de Feraudy Yvan
Mariani Odette
Nicolas André
Meyniel Jean-Philippe
Cottu Paul
Sastre-Garau Xavier
Mechta-Grigoriou Fatima
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.2512
Published
2011-11-20
Epub
2011-00-20
Pages
1627-35
Language
English
Region
United States
NLM ID
9502015
Subset
IM
Databases
GEO
GSE26113, GSE26193, GSE26194
Corrections
CommentIn
PMID: 22146456
External Links
PubMed source DOI: 10.1038/nm.2512 View journal details
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