The miR-200 family and miR-205 are repressed by Twist1 and concurrently silenced and DNA hypermethylated in invasive bladder cancer

Research output: Contribution to conferencePosterResearch

  • Erik Digman Wiklund, Denmark
  • Department of Molecular Biology

MicroRNAs (miRNA) are small non-coding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and miR-205 are encoded in three separate genomic loci and are frequently silenced in advanced cancer. The miR-200 family and miR-205 have been implicated in tumour invasion and metastasis by negatively regulating the transcriptional repressors of E-cadherin, ZEB1 and ZEB2. Loss of miR-200 expression leads to silencing of E-cadherin, thereby promoting epithelial to mesenchymal transition (EMT) and loss of cell adhesion. However, little is known about the transcriptional regulation of the miR-200s. Here we show that the three miR-200 loci are concurrently silenced and gain promoter hypermethylation in muscle invasive bladder tumors and undifferentiated bladder cell lines. Furthermore, we report that the mesoderm transcription factor Twist1 and miR-200 expression is inversely correlated, and that Twist1 represses miR-200 expression in the normal bladder cell line HU609 by directly binding to E-box motifs in the miR-200 family and miR-205 promoters.  This is the first implication of a role for Twist1 in transcriptional repression of miRNAs and the first report demonstrating concerted transcriptional regulation of the three miR-200 loci. Our data also indicate that DNA hypermethylation of the miR-200 family and miR-205 are possible prognostic markers in bladder cancer.  

Original languageEnglish
Publication year2010
Publication statusPublished - 2010
EventKeystone Symposia - RNA Silencing: Mechanism, Biology and Application - Keystone, United States
Duration: 14 Jan 201019 Jan 2010
Conference number: A7

Conference

ConferenceKeystone Symposia - RNA Silencing: Mechanism, Biology and Application
NumberA7
CountryUnited States
CityKeystone
Period14/01/201019/01/2010

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