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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Terapia celular > DA - CIMA - Oncología - Terapia celular - Artículos de Revista >

Epigenetic regulation of microRNA expression in colorectal cancer
Authors: Bandres, E. (Eva)
Aguirre, X. (Xavier)
Bitarte, N. (Nerea)
Ramirez, N. (Natalia)
Zarate, R. (Ruth)
Roman-Gomez, J. (José)
Prosper, F. (Felipe)
Garcia-Foncillas, J. (Jesús)
Keywords: Materias Investigacion::Ciencias de la Salud::Oncología
Issue Date: 2009
Publisher: Wiley-Blackwell
Publisher version: http://dx.doi.org/10.1002/ijc.24638
ISSN: 0020-7136
Citation: Bandrés, E., Agirre, X., Bitarte, N., Ramírez, N. et al. Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer. 2009; 125(11): 2737-43.
Abstract
In the last years, microRNAs (miRNA) have emerged as new molecular players involved in carcinogenesis. Deregulation of miRNAs expression has been shown in different human cancer but the molecular mechanism underlying the alteration of miRNA expression is unknown. To identify tumor-supressor miRNAs silenced through aberrant epigenetic events in colorectal cancer (CRC), we used a sequential approach. We first identified 5 miRNAs down-regulated in colorectal cancer patient samples and located around/on a CpG island. Treatment with a DNA methyltransferase inhibitor and a HDAC inhibitor restored expression of 3 of the 5 microRNAs (hsa-miR-9, hsa-miR-129 and hsa-miR-137) in 3 CRC cell lines. Expression of hsa-miR-9 was inversely correlated with methylation of their promoter regions as measure by MSP and bisulphate sequencing. Further, methylation of the hsa-miR-9-1, hsa-miR-129-2 and hsa-miR- 137 CpG islands were frequently observed in CRC cell lines and in primary CRC tumors, but not in normal colonic mucosa. Finally, methylation of hsa-miR-9-1 was associated with the presence of lymph node metastasis. In summary, our results aid in the understanding of miRNA gene regulation showing that aberrant DNA methylation and histone modifications work together to induce silencing of miRNAs in CRC.
Permanent link: http://hdl.handle.net/10171/17938
Appears in Collections:DA - CIMA - Oncología - Síndromes mieloproliferativos - Artículos de Revista
DA - CIMA - Oncología - Terapia celular - Artículos de Revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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