title: MicroRNA-27a Indirectly Regulates Estrogen Receptor {alpha} Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells.
abstract: MicroRNA-27a (miR-27a) is expressed in MCF-7 breast cancer cells, and antisense miR-27a (as-miR-27a) induces ZBTB10, a specificity protein (Sp) repressor. Both as-miR-27a and overexpression of ZBTB10 decreased Sp1, Sp3, and Sp4 mRNA and protein expression in MCF-7 cells, and this was also accompanied by decreased levels of estrogen receptor alpha (ERalpha) mRNA and protein. RNA interference studies confirmed that basal expression of ERalpha was dependent on Sp1 but not Sp3 or Sp4 in MCF-7 cells. as-miR-27a and overexpression of ZBTB10 inhibited 17beta-estradiol (E2)-induced transactivation in MCF-7 cells, and this was accompanied by decreased binding of Sp and ER proteins in cell lysates to oligonucleotides containing GC-rich motifs or estrogen-responsive elements, respectively. as-miR-27a and overexpression of ZBTB10 arrested MCF-7 cells in G(0)/G(1) and inhibited E2-induced G(0)/G(1) to S phase progression. as-miR-27a induced only a minimal increase in Myt-1, another miR-27a regulated gene, and this was not accompanied by Myt-1-dependent G(2)/M arrest as observed previously in ER-negative MDA-MB-231 breast cancer cells. Thus, miR-27a indirectly regulates E2-responsiveness in MCF-7 cells through suppression of ZBTB10, thereby enhancing expression of ERalpha.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, College Station, Texas 77843-4466, USA.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Li
authors.forename: Susanne U
authors.initials: SU
authors.lastname: Mertens-Talcott
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Kyounghyun
authors.initials: K
authors.lastname: Kim
authors.forename: Judith
authors.initials: J
authors.lastname: Ball
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D034622:RNA Interference / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051704:Sp2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051706:Sp4 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D051706:Sp4 Transcription Factor; D051704:Sp2 Transcription Factor; D004958:Estradiol
references.citation: J Biol Chem. 2001 Oct 5;276(40):36869-72
references.pmid: 11459850
references.citation: Endocrinology. 2003 Jun;144(6):2325-35
references.pmid: 12746293
references.citation: J Natl Cancer Inst. 2006 Jun 21;98(12):855-68
references.pmid: 16788159
references.citation: Cancer Res. 2001 May 15;61(10):4143-54
references.pmid: 11358838
references.citation: J Steroid Biochem Mol Biol. 2000 Nov 30;74(5):311-7
references.pmid: 11162939
references.citation: Biochem Biophys Res Commun. 2006 Jun 23;345(1):292-301
references.pmid: 16678129
references.citation: Prog Nucleic Acid Res Mol Biol. 2004;77:1-36
references.pmid: 15196889
references.citation: Cancer Res. 2007 Apr 1;67(7):3286-94
references.pmid: 17409437
references.citation: Mol Interv. 2003 Aug;3(5):281-92
references.pmid: 14993442
references.citation: J Mol Endocrinol. 2007 Oct;39(4):289-304
references.pmid: 17909268
references.citation: Mol Endocrinol. 2007 Dec;21(12):2988-3001
references.pmid: 17717078
references.citation: Mol Cell Endocrinol. 2002 Sep 30;195(1-2):27-38
references.pmid: 12354670
references.citation: Endocrinology. 2003 Oct;144(10):4562-74
references.pmid: 12959972
references.citation: Eur J Cancer. 2005 Nov;41(16):2438-48
references.pmid: 16209919
references.citation: Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):4109-17
references.pmid: 15217947
references.citation: Oncogene. 2006 Jun 1;25(23):3296-306
references.pmid: 16462771
references.citation: Mol Cancer Ther. 2008 Mar;7(3):464-73
references.pmid: 18347134
references.citation: BMC Genomics. 2008 Oct 11;9:476
references.pmid: 18847501
references.citation: Cancer Res. 2006 Feb 1;66(3):1277-81
references.pmid: 16452179
references.citation: J Biol Chem. 2008 Nov 7;283(45):31079-86
references.pmid: 18790736
references.citation: Cell. 1986 Sep 26;46(7):1053-61
references.pmid: 3463433
references.citation: J Biol Chem. 1999 Mar 19;274(12):8123-8
references.pmid: 10075714
references.citation: Cancer Res. 2005 Feb 1;65(3):1007-17
references.pmid: 15705902
references.citation: Mol Cell Biol. 1996 Apr;16(4):1687-94
references.pmid: 8657144
references.citation: J Biol Chem. 2000 Feb 25;275(8):5379-87
references.pmid: 10681512
references.citation: J Cell Physiol. 2001 Aug;188(2):143-60
references.pmid: 11424081
references.citation: Crit Rev Biochem Mol Biol. 2002;37(1):1-28
references.pmid: 11905545
references.citation: Biochem Biophys Res Commun. 2007 Feb 2;353(1):86-91
references.pmid: 17161377
references.citation: Oncogene. 1997 Aug 7;15(6):669-76
references.pmid: 9264407
references.citation: Cancer Res. 1997 Aug 1;57(15):3071-8
references.pmid: 9242427
references.citation: Breast Cancer Res Treat. 2004 May;85(2):111-20
references.pmid: 15111769
references.citation: BMC Cancer. 2002 Dec 10;2:35
references.pmid: 12475396
references.citation: Mol Cell Endocrinol. 1999 Nov 25;157(1-2):1-9
references.pmid: 10619392
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13994-9
references.pmid: 14610279
references.citation: Cancer Res. 2007 Mar 15;67(6):2816-23
references.pmid: 17363604
references.citation: Biochem Pharmacol. 1999 Mar 15;57(6):597-601
references.pmid: 10037443
references.citation: Cancer Res. 2000 Mar 15;60(6):1546-51
references.pmid: 10749121
references.citation: Cell. 1997 May 16;89(4):619-28
references.pmid: 9160753
references.citation: J Steroid Biochem Mol Biol. 2002 Sep;82(1):7-18
references.pmid: 12429135
references.citation: Clin Cancer Res. 2003 Dec 15;9(17):6371-80
references.pmid: 14695137
references.citation: Mol Endocrinol. 2007 May;21(5):1132-47
references.pmid: 17312270
references.citation: Cancer Res. 2004 Sep 15;64(18):6740-9
references.pmid: 15374992
references.citation: Mol Endocrinol. 2005 Jun;19(6):1402-11
references.pmid: 15914709
references.citation: Cell. 1983 Nov;35(1):79-87
references.pmid: 6313230
references.citation: Cancer Res. 2007 Nov 15;67(22):11001-11
references.pmid: 18006846
references.citation: J Biol Chem. 2001 Oct 5;276(40):36863-4
references.pmid: 11459855