دورية أكاديمية
Histone demethylase PHF8 promotes epithelial to mesenchymal transition and breast tumorigenesis.
العنوان: | Histone demethylase PHF8 promotes epithelial to mesenchymal transition and breast tumorigenesis. |
---|---|
المؤلفون: | Shao P; Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, IA 52242, USA., Liu Q; Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, IA 52242, USA., Maina PK; Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, IA 52242, USA., Cui J; Department of Histology and Embryology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China., Bair TB; Iowa Institute of Human Genetics, Carver College of Medicine, The University of Iowa, IA 52242, USA., Li T; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA., Umesalma S; Department of Pathology, Carver College of Medicine, The University of Iowa, IA 52242, USA., Zhang W; Department of Pathology, Carver College of Medicine, The University of Iowa, IA 52242, USA., Qi HH; Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, IA 52242, USA. |
المصدر: | Nucleic acids research [Nucleic Acids Res] 2017 Feb 28; Vol. 45 (4), pp. 1687-1702. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1992- : Oxford : Oxford University Press Original Publication: London, Information Retrieval ltd. |
مواضيع طبية MeSH: | Epithelial-Mesenchymal Transition*/drug effects , Epithelial-Mesenchymal Transition*/genetics, Breast Neoplasms/*metabolism , Cell Transformation, Neoplastic/*metabolism , Histone Demethylases/*metabolism , Histones/*metabolism , Transcription Factors/*metabolism, Animals ; Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Signal Transduction ; Transcriptional Activation ; Transforming Growth Factor beta/pharmacology |
مستخلص: | Histone demethylase PHF8 is upregulated and plays oncogenic roles in various cancers; however, the mechanisms underlying its dysregulation and functions in carcinogenesis remain obscure. Here, we report the novel functions of PHF8 in EMT (epithelial to mesenchymal transition) and breast cancer development. Genome-wide gene expression analysis revealed that PHF8 overexpression induces an EMT-like process, including the upregulation of SNAI1 and ZEB1. PHF8 demethylates H3K9me1, H3K9me2 and sustains H3K4me3 to prime the transcriptional activation of SNAI1 by TGF-β signaling. We show that PHF8 is upregulated and positively correlated with MYC at protein levels in breast cancer. MYC post-transcriptionally regulates the expression of PHF8 via the repression of microRNAs. Specifically, miR-22 directly targets and inhibits PHF8 expression, and mediates the regulation of PHF8 by MYC and TGF-β signaling. This novel MYC/microRNAs/PHF8 regulatory axis thus places PHF8 as an important downstream effector of MYC. Indeed, PHF8 contributes to MYC-induced cell proliferation and the expression of EMT-related genes. We also report that PHF8 plays important roles in breast cancer cell migration and tumor growth. These oncogenic functions of PHF8 in breast cancer confer its candidacy as a promising therapeutic target for this disease. (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.) |
References: | Mol Cell. 2007 Aug 17;27(4):585-95. (PMID: 17707230) Mol Cell. 2010 Apr 23;38(2):165-78. (PMID: 20346720) Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):992-9. (PMID: 11158583) Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):7731-6. (PMID: 26056275) Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) Nature. 2011 Feb 24;470(7335):548-53. (PMID: 21326202) Nucleic Acids Res. 2014 Jan;42(Database issue):D92-7. (PMID: 24297251) Am J Cancer Res. 2015 Mar 15;5(4):1519-30. (PMID: 26101715) Nature. 2010 Jul 22;466(7305):508-12. (PMID: 20622854) Sci Signal. 2010 Apr 13;3(117):ra29. (PMID: 20388916) Oncogene. 2012 Jul 19;31(29):3444-56. (PMID: 22120715) Respir Res. 2005 Jun 09;6:56. (PMID: 15946381) Cell. 2012 Mar 30;149(1):22-35. (PMID: 22464321) eNeuro. 2015 Mar 14;2(1):null. (PMID: 26464965) Oncogene. 2010 Sep 2;29(35):4980-8. (PMID: 20562918) Nat Rev Mol Cell Biol. 2012 Oct;13(10):616-30. (PMID: 22992590) Cell. 2012 Nov 21;151(5):937-50. (PMID: 23178117) Nature. 2010 Jul 22;466(7305):503-7. (PMID: 20622853) Nat Rev Cancer. 2003 Nov;3(11):807-21. (PMID: 14557817) Nat Struct Mol Biol. 2010 Apr;17(4):445-50. (PMID: 20208542) Nat Genet. 2008 Jan;40(1):43-50. (PMID: 18066065) Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15449-54. (PMID: 20713713) Nature. 2012 Sep 6;489(7414):57-74. (PMID: 22955616) Cell Rep. 2014 Mar 13;6(5):868-77. (PMID: 24582965) Nat Genet. 2007 Oct;39(10):1278-84. (PMID: 17893677) Neoplasia. 2004 Jan-Feb;6(1):1-6. (PMID: 15068665) Mol Cell Biol. 2010 Jul;30(13):3286-98. (PMID: 20421419) Nat Genet. 2003 Jul;34(3):267-73. (PMID: 12808457) Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96. (PMID: 24556840) Cell. 2011 Sep 16;146(6):904-17. (PMID: 21889194) Cancer Lett. 2010 Jul 28;293(2):230-9. (PMID: 20144848) Nucleic Acids Res. 2012 Oct;40(19):9429-40. (PMID: 22850744) Biochem Biophys Res Commun. 2014 Aug 15;451(1):119-25. (PMID: 25065740) Nat Rev Genet. 2012 Apr 03;13(5):343-57. (PMID: 22473383) Cell Mol Life Sci. 2008 Nov;65(23):3756-88. (PMID: 18726070) PLoS One. 2013 Oct 11;8(10):e77353. (PMID: 24146981) Elife. 2015 Aug 12;4:null. (PMID: 26267216) J Biol Chem. 2012 Dec 28;287(53):44508-17. (PMID: 23152497) Mol Cell. 2012 Nov 9;48(3):445-58. (PMID: 23022380) PLoS One. 2012;7(12):e51136. (PMID: 23251436) J Med Chem. 2013 Sep 26;56(18):7222-31. (PMID: 23964788) Methods. 2003 Jul;30(3):256-68. (PMID: 12798140) CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. (PMID: 26742998) Cancer Cell. 2013 Mar 18;23 (3):376-89. (PMID: 23518351) J Clin Invest. 2016 Jun 1;126(6):2205-20. (PMID: 27183383) Oncogene. 2009 Jan 22;28(3):422-30. (PMID: 18978814) |
معلومات مُعتمدة: | P30 CA086862 United States CA NCI NIH HHS; R01 CA200673 United States CA NCI NIH HHS; R01 CA203834 United States CA NCI NIH HHS; UL1 RR024979 United States RR NCRR NIH HHS |
المشرفين على المادة: | 0 (Histones) 0 (MicroRNAs) 0 (Proto-Oncogene Proteins c-myc) 0 (Transcription Factors) 0 (Transforming Growth Factor beta) EC 1.14.11.- (Histone Demethylases) EC 1.14.11.- (PHF8 protein, human) |
تواريخ الأحداث: | Date Created: 20161201 Date Completed: 20171002 Latest Revision: 20181113 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC5389682 |
DOI: | 10.1093/nar/gkw1093 |
PMID: | 27899639 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1362-4962 |
---|---|
DOI: | 10.1093/nar/gkw1093 |