دورية أكاديمية
Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer.
| العنوان: | Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. |
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| المؤلفون: | Wiklund ED; Department of Molecular Biology, Aarhus University, Aarhus C, Denmark., Bramsen JB, Hulf T, Dyrskjøt L, Ramanathan R, Hansen TB, Villadsen SB, Gao S, Ostenfeld MS, Borre M, Peter ME, Ørntoft TF, Kjems J, Clark SJ |
| المصدر: | International journal of cancer [Int J Cancer] 2011 Mar 15; Vol. 128 (6), pp. 1327-34. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1995- : New York, NY : Wiley-Liss Original Publication: 1966-1984 : Genève : International Union Against Cancer |
| مواضيع طبية MeSH: | Epigenomics*, MicroRNAs/*genetics , Urinary Bladder Neoplasms/*genetics, Cells, Cultured ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Urinary Bladder/metabolism ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/pathology |
| مستخلص: | MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and miR-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. ZEB1 is also known to repress miR-200c-141 transcription in a negative feedback loop, but otherwise little is known about the transcriptional regulation of the miR-200 family and miR-205. Recently, miR-200 silencing was also reported in cancer stem cells, implying that miR-200 deregulation is a key event in multiple levels of tumor biology. However, what prevents miR-200 expression remains largely unanswered. Here we report concerted transcriptional regulation of the miR-200 and miR-205 loci in bladder tumors and bladder cell lines. Using a combination of miRNA expression arrays, qPCR assays and mass spectrometry DNA methylation analyses, we show that the miR-200 and miR-205 loci are specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines. Moreover, we report that miR-200c expression is significantly correlated with early stage T1 bladder tumor progression, and propose miR-200 and miR-205 silencing and DNA hypermethylation as possible prognostic markers in bladder cancer. In addition, we observe that the mesoderm transcription factor TWIST1 and miR-200 expression are inversely correlated in bladder tumor samples and cell lines. TWIST1 associates directly with the miR-200 and miR-205 promoters, and may act as a repressor of miR-200 and miR-205 expression. (Copyright © 2010 UICC.) |
| المشرفين على المادة: | 0 (MIRN200 microRNA, human) 0 (MIRN205 microRNA, human) 0 (MicroRNAs) |
| تواريخ الأحداث: | Date Created: 20100518 Date Completed: 20110324 Latest Revision: 20220410 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1002/ijc.25461 |
| PMID: | 20473948 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1097-0215 |
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| DOI: | 10.1002/ijc.25461 |