title: miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response.
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.
authors.affiliation: Stress and Cancer Laboratory, Institut Curie, Paris, France.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Mateescu
authors.forename: Luciana
authors.initials: L
authors.lastname: Batista
authors.forename: Melissa
authors.initials: M
authors.lastname: Cardon
authors.forename: Tina
authors.initials: T
authors.lastname: Gruosso
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Feraudy
authors.forename: Odette
authors.initials: O
authors.lastname: Mariani
authors.forename: André
authors.initials: A
authors.lastname: Nicolas
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Meyniel
authors.forename: Paul
authors.initials: P
authors.lastname: Cottu
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Fatima
authors.initials: F
authors.lastname: Mechta-Grigoriou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D018384:Oxidative Stress
chemical_list: C533895:MIRN141 microRNA, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C543718:Mirn141 microRNA, mouse; C543719:Mirn200 microRNA, mouse; D048308:Mitogen-Activated Protein Kinase 14
references.citation: Mol Cancer Ther. 2010 May;9(5):1080-91
references.pmid: 20442302
references.citation: Gynecol Oncol. 2010 May;117(2):170-6
references.pmid: 20132968
references.citation: Cancer Res. 2008 Jan 15;68(2):425-33
references.pmid: 18199536
references.citation: Mol Cell. 2010 Jun 25;38(6):908-15
references.pmid: 20620960
references.citation: J Cell Mol Med. 2008 Sep-Oct;12(5A):1426-31
references.pmid: 18624759
references.citation: J Biol Chem. 2009 Mar 20;284(12):7903-13
references.pmid: 19158092
references.citation: Cancer Cell. 2007 Feb;11(2):101-3
references.pmid: 17292820
references.citation: J Oncol. 2010;2010:821717
references.pmid: 20049172
references.citation: Gynecol Oncol. 2009 Aug;114(2):253-9
references.pmid: 19446316
references.citation: J Immunol. 2009 Jun 1;182(11):7048-57
references.pmid: 19454702
references.citation: Cancer Res. 2007 Apr 15;67(8):3512-7
references.pmid: 17440056
references.citation: Genes Dev. 2009 Sep 15;23(18):2152-65
references.pmid: 19759263
references.citation: Cell Metab. 2008 Feb;7(2):113-24
references.pmid: 18249171
references.citation: Clin Cancer Res. 2008 May 1;14(9):2690-5
references.pmid: 18451233
references.citation: Biol Chem. 2006 Oct-Nov;387(10-11):1337-46
references.pmid: 17081104
references.citation: Free Radic Biol Med. 2000 Feb 1;28(3):463-99
references.pmid: 10699758
references.citation: Cancer Metastasis Rev. 2010 Jun;29(2):351-78
references.pmid: 20386957
references.citation: Genes Dev. 2009 Sep 15;23(18):2140-51
references.pmid: 19759262
references.citation: Cell Death Differ. 2011 Oct;18(10):1628-39
references.pmid: 21527937
references.citation: Nature. 2011 Jun 29;474(7353):609-15
references.pmid: 21720365
references.citation: Cancer Res. 2007 Sep 1;67(17):7972-6
references.pmid: 17804704
references.citation: Nat Genet. 2007 Jun;39(6):741-9
references.pmid: 17468757
references.citation: Lancet Oncol. 2011 Mar;12(3):273-85
references.pmid: 21345725
references.citation: Int J Biochem Cell Biol. 2010 Aug;42(8):1282-90
references.pmid: 20083225
references.citation: Cell. 2007 Oct 5;131(1):136-45
references.pmid: 17923093
references.citation: Cancer Res. 2007 Sep 15;67(18):8699-707
references.pmid: 17875710
references.citation: Gynecol Oncol. 2009 Sep;114(3):457-64
references.pmid: 19501389
references.citation: J Cell Biol. 2009 Apr 6;185(1):115-27
references.pmid: 19332888
references.citation: Cancer Res. 2008 Oct 1;68(19):7846-54
references.pmid: 18829540
references.citation: EMBO Mol Med. 2010 Jun;2(6):211-30
references.pmid: 20535745
references.citation: J Exp Med. 2011 May 9;208(5):875-83
references.pmid: 21518799
references.citation: Nature. 2011 Jul 13;475(7355):231-4
references.pmid: 21753854
references.citation: Nat Cell Biol. 2011 Mar;13(3):317-23
references.pmid: 21336307
references.citation: Cell. 2009 Aug 7;138(3):592-603
references.pmid: 19665978
references.citation: Endocr Relat Cancer. 2010 Dec 21;18(1):85-95
references.pmid: 21051560
references.citation: Mol Cell. 2010 Sep 10;39(5):761-72
references.pmid: 20832727
references.citation: Cancer Res. 2006 Nov 15;66(22):10843-8
references.pmid: 17108120
references.citation: EMBO Rep. 2008 Jun;9(6):582-9
references.pmid: 18483486
references.citation: Genes Dev. 2008 Apr 1;22(7):894-907
references.pmid: 18381893
references.citation: Nat Cell Biol. 2009 Dec;11(12):1487-95
references.pmid: 19935649
references.citation: Cell Mol Life Sci. 2009 Dec;66(23):3663-73
references.pmid: 19629388
references.citation: PLoS One. 2009 Jul 27;4(7):e6377
references.pmid: 19633716
references.citation: Int J Cancer. 2011 Mar 15;128(6):1327-34
references.pmid: 20473948
references.citation: Nat Rev Cancer. 2009 Aug;9(8):537-49
references.pmid: 19629069
references.citation: Cancer Cell. 2007 Feb;11(2):191-205
references.pmid: 17292829
references.citation: Cell. 2004 Sep 17;118(6):781-94
references.pmid: 15369676
references.citation: Lancet. 2009 Oct 17;374(9698):1371-82
references.pmid: 19793610
references.citation: Cell. 2009 Dec 11;139(6):1096-108
references.pmid: 20005803
references.citation: Brain Res. 2010 Jul 30;1346:14-25
references.pmid: 20510889
references.citation: Nat Cell Biol. 2008 May;10(5):593-601
references.pmid: 18376396
references.citation: Cell Death Differ. 2008 Jan;15(1):89-93
references.pmid: 17762881
references.citation: PLoS One. 2009;4(4):e5311
references.pmid: 19390579
references.citation: Cancer Res. 2005 Sep 15;65(18):8455-60
references.pmid: 16166325
references.citation: J Biol Chem. 2008 May 30;283(22):14910-4
references.pmid: 18411277
references.citation: Int J Biochem Cell Biol. 2010 Aug;42(8):1262-72
references.pmid: 20035894
references.citation: BMC Med Genomics. 2008 Nov 28;1:59
references.pmid: 19038057
references.citation: Gynecol Oncol. 2010 Jan;116(1):117-25
references.pmid: 19854497
references.citation: BMC Cancer. 2010 May 21;10:222
references.pmid: 20492709
references.citation: Biochim Biophys Acta. 2010 Apr;1802(4):396-405
references.pmid: 20079433
references.citation: Clin Cancer Res. 2008 Aug 15;14(16):5198-208
references.pmid: 18698038