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.) |
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| 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 |
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