role for dna methylation in the regulation of mir-200c and mir-141 expression in normal and cancer cellsdna甲基化作用的调节mir - 200 c和mir - 141表达在正常和肿瘤细胞.pdfVIP

Role for DNA Methylation in the Regulation of miR-200c and miR-141 Expression in Normal and Cancer Cells 1,4 1,2 3 1 1 1 Lukas Vrba , Taylor J. Jensen , James C. Garbe , Ronald L. Heimark , Anne E. Cress , Sally Dickinson , Martha R. Stampfer1,3, Bernard W. Futscher1,2* 1 Arizona Cancer Center, The University of Arizona, Tucson, Arizona, United States of America, 2 Department of Pharmacology Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona, United States of America, 3 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America, 4 Biology Centre ASCR, v.v.i., Institute of Plant Molecular Biology, Ceske Budejovice, Czech Republic Abstract Background: The microRNA-200 family participates in the maintenance of an epithelial phenotype and loss of its expression can result in epithelial to mesenchymal transition (EMT). Furthermore, the loss of expression of miR-200 family members is linked to an aggressive cancer phenotype. Regulation of the miR-200 family expression in normal and cancer cells is not fully understood. Methodology/Principal Findings: Epigenetic mechanisms participate in the control of miR-200c and miR-141 expression in both normal and cancer cells. A CpG island near the predicted mir-200c/mir-141 transcription start site shows a striking correlation between miR-200c and miR-141 expression and DNA methylation in both normal and cancer cells, as determined by MassARRAY technology. The CpG island is unmethylated in human miR-200/miR-141 expressing epithelial cells and in miR-200c/miR-141 positive tumor cells. The CpG island is heavily methylated in human miR-200c/miR-141 negative fibroblasts and miR-