Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression (Cancer Cell, 2008, 13:496-506)

報告日期: 2008/11/14
報告時間: 16:00/16:50
報告學生: 陳怡成
講評老師: 賴明德

Genetic and Epigenetic Silencing of MicroRNA-203

Enhances ABL1 and BCR-ABL1 Oncogene Expression


Marı́a J. Bueno, Ignacio Pérez de Castro, Marta Gómez de Cedrón, Javier Santos, George A. Calin, Juan C. Cigudosa, Carlo M. Croce, JoséFernández-Piqueras, and Marcos Malumbres


Cancer Cell 13, 496–506, June 2008




Date : 11/14, 2008 (17:00~18:00)

Place : 602


Abstract :



MicroRNAs (miRNAs) are noncoding RNAs that regulate many cellular functions including cell proliferation, differentiation, and apoptosis by silencing specific target genes through translational repression or direct mRNA degradation. In the last few years, it has become evident that miRNA expression is deregulated in human cancer, resulting in specific oncogenic events. Specific over- or underexpression has been shown to correlate with particular tumor types. These changes in expression might modulate known oncogenes or tumor suppressors. In this study, we have identified a region of mouse chromosome 12 (F2 region, conserved in human chromosome 14q32) that is frequently lost in T cell malignancies. This chromosomal region is especially rich in microRNAs, since it contains several clusters of microRNAs and expresses 52 mature microRNAs. We have narrowed down the fragile site to a region of about 7 Mb that contains 51 out of these 52 miRNAs. We have detected significant silencing of one of these miRNAs, miR-203. Since affected tumors usually lose only one copy of this DNA region. The authors demonstrate that ABL1 is a direct target of miR-203, miR-203 is silenced by genetic and epigenetic mechanisms in hematopoietic malignancies expressing either ABL1 or BCR-ABL1, and reexpression of miR-203 reduces ABL1 and BCR-ABL1 fusion protein levels and inhibits tumor cell proliferation in an ABL1-dependent manner. Thus, miR-203 functions as a tumor suppressor, and re-expression of this microRNA might have therapeutic benefits in specific hematopoietic malignancies.