Epigenetic silencing of miR-181c by DNA methylation in glioblastoma cell lines
| Autor: | Karin Meier, Georgina Guerrero, Rodrigo G. Arzate-Mejía, Erandi Ayala-Ortega, Rosario Pérez-Molina, Edgar González-Buendía, Félix Recillas-Targa |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cancer Research CCCTC-Binding Factor Epigenetic regulation of neurogenesis Biology medicine.disease_cause Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Epigenetics of physical exercise RNA interference Cell Line Tumor microRNA medicine Genetics Biomarkers Tumor Humans Epigenetics Gene Silencing Receptor Notch2 DNA methylation Glioblastoma cells Cell biology Gene Expression Regulation Neoplastic Repressor Proteins MicroRNAs 030104 developmental biology Oncology CTCF 030220 oncology & carcinogenesis CCCTC-binding factor (CTCF) Carcinogenesis Glioblastoma Chromatin immunoprecipitation Research Article |
| Zdroj: | BMC Cancer |
| ISSN: | 1471-2407 |
| Popis: | Background Post-transcriptional regulation by microRNAs is recognized as one of the major pathways for the control of cellular homeostasis. Less well understood is the transcriptional and epigenetic regulation of genes encoding microRNAs. In the present study we addressed the epigenetic regulation of the miR-181c in normal and malignant brain cells. Methods To explore the epigenetic regulation of the miR-181c we evaluated its expression using RT-qPCR and the in vivo binding of the CCCTC-binding factor (CTCF) to its regulatory region in different glioblastoma cell lines. DNA methylation survey, chromatin immunoprecipitation and RNA interference assays were used to assess the role of CTCF in the miR-181c epigenetic silencing. Results We found that miR-181c is downregulated in glioblastoma cell lines, as compared to normal brain tissues. Loss of expression correlated with a notorious gain of DNA methylation at the miR-181c promoter region and the dissociation of the multifunctional nuclear factor CTCF. Taking advantage of the genomic distribution of CTCF in different cell types we propose that CTCF has a local and cell type specific regulatory role over the miR-181c and not an architectural one through chromatin loop formation. This is supported by the depletion of CTCF in glioblastoma cells affecting the expression levels of NOTCH2 as a target of miR-181c. Conclusion Together, our results point to the epigenetic role of CTCF in the regulation of microRNAs implicated in tumorigenesis. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2273-6) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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