title: miR-221 promotes tumorigenesis in human triple negative breast cancer cells.
abstract: Patients with triple-negative breast cancers (TNBCs) typically have a poor prognosis. TNBCs are characterized by their resistance to apoptosis, aggressive cellular proliferation, migration and invasion, and currently lack molecular markers and effective targeted therapy. Recently, miR-221/miR-222 have been shown to regulate ERα expression and ERα-mediated signaling in luminal breast cancer cells, and also to promote EMT in TNBCs. In this study, we characterized the role of miR-221 in a panel of TNBCs as compared to other breast cancer types. miR-221 knockdown not only blocked cell cycle progression, induced cell apoptosis, and inhibited cell proliferation in-vitro but it also inhibited in-vivo tumor growth by targeting p27(kip1). Furthermore, miR-221 knockdown inhibited cell migration and invasion by altering E-cadherin expression, and its regulatory transcription factors Snail and Slug in human TNBC cell lines. Therefore, miR-221 functions as an oncogene and is essential in regulating tumorigenesis in TNBCs both in vitro as well as in vivo.
authors: Oncology Research, Pfizer Worldwide Research and Development, San Diego, California, United States of America.
authors: Rounak
authors: R
authors: Nassirpour
authors: Pramod P
authors: PP
authors: Mehta
authors: Sangita M
authors: SM
authors: Baxi
authors: Min-Jean
authors: MJ
authors: Yin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000235:genetics
chemical_list: D015820:Cadherins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C525709:MIR221, human; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse
references: Nat Rev Mol Cell Biol. 2004 Nov;5(11):897-907
references: 15520809
references: Nature. 2005 Feb 17;433(7027):769-73
references: 15685193
references: Breast Cancer Res Treat. 2012 Feb;132(1):75-85
references: 21553120
references: Pathology. 2009 Jan;41(1):40-7
references: 19089739
references: J Biol Chem. 2010 Aug 27;285(35):26900-26907
references: 20576614
references: Int J Oncol. 2010 Dec;37(6):1621-6
references: 21042732
references: Nat Rev Cancer. 2006 Apr;6(4):259-69
references: 16557279
references: Oncogene. 2011 Mar 3;30(9):1082-97
references: 21057537
references: BMC Cancer. 2012 Oct 02;12:445
references: 23031797
references: Cell Mol Life Sci. 2012 Oct;69(20):3429-56
references: 22945800
references: Nature. 2005 Jun 9;435(7043):834-8
references: 15944708
references: Cancer Res. 2002 Mar 15;62(6):1613-8
references: 11912130
references: Cancer Cell. 2009 Dec 8;16(6):498-509
references: 19962668
references: JAMA. 2006 Jun 7;295(21):2492-502
references: 16757721
references: Cell Cycle. 2010 Jun 15;9(12):2342-52
references: 20519948
references: J Biol Chem. 2008 Oct 31;283(44):29897-903
references: 18708351
references: EMBO J. 2007 Aug 8;26(15):3699-708
references: 17627278
references: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999-3004
references: 14973191
references: Cancer Res. 2009 Apr 15;69(8):3356-63
references: 19351832
references: Curr Opin Obstet Gynecol. 2008 Feb;20(1):40-6
references: 18197004
references: J Biol Chem. 2007 Aug 10;282(32):23716-24
references: 17569667
references: Nature. 2000 Aug 17;406(6797):747-52
references: 10963602
references: Cell Cycle. 2011 Feb 1;10(3):507-17
references: 21270527
references: J Biol Chem. 2008 Nov 7;283(45):31079-86
references: 18790736
references: J Mammary Gland Biol Neoplasia. 2012 Mar;17(1):65-77
references: 22350980
references: Clin Cancer Res. 2009 Aug 15;15(16):5073-81
references: 19671867
references: Sci Signal. 2011 Jun 14;4(177):ra41
references: 21673316
references: Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34
references: 17671126
references: Oncogene. 2008 Sep 25;27(43):5651-61
references: 18521080
references: Horm Cancer. 2010 Dec;1(6):306-19
references: 21761362
references: Ann Oncol. 2007 Jul;18(7):1285-6
references: 17675400
references: Cell. 2009 Nov 25;139(5):871-90
references: 19945376
references: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74
references: 11553815
references: Nature. 2004 Sep 16;431(7006):350-5
references: 15372042
references: Cell. 2003 Dec 26;115(7):787-98
references: 14697198
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: Nat Rev Mol Cell Biol. 2010 Sep;11(9):621-32
references: 20683470
references: Nat Rev Cancer. 2006 Nov;6(11):857-66
references: 17060945
references: J Biol Chem. 2011 Dec 9;286(49):42292-42302
references: 22009755