Tuesday, 10 June 2008

MicroRNA Controls Expression of Oncogenes

MicroRNA Controls Expression of Oncogenes Tuesday, 10 June 2008 A new study demonstrates that microRNAs can modulate the expression of well known tumour-specific oncogenic translocation proteins and may play a significant role in some human cancers. The research, published by Cell Press in the June issue of the journal Cancer Cell, is likely to lead to new strategies for treating some specific lymphomas and leukaemia’s. MicroRNAs (miRNAs) are small non-coding pieces of RNA that can modulate the expression of specific target genes. Recent studies have suggested that increases or decreases in miRNA expression may be linked with regulation of oncogenes or tumour suppressors and are therefore likely to play an important role in human cancers. Dr. Marcos Malumbres from the Spanish National Cancer Research Center (CNIO) in Madrid, Spain and colleagues identified a miRNA-rich chromosomal region in mice that is frequently lost in T cell malignancies. This particular region encodes about 12% of all genomic miRNAs. The researchers used miRNA expression profiling to reveal that one particular miRNA, miR-203, is silenced by both genetic and epigenetic mechanisms in several mouse and human blood cell malignancies, including chronic myelogenous leukaemia’s and some acute lymphoblastic leukaemia’s. The researchers went on to show that transcriptional silencing of miR-203 lead to up-regulation of the oncogene ABL1 and the BCR-ABL1 oncogenic fusion protein in various mouse and human hematopoietic malignancies. Further, restoration of miR-203 resulted in a subsequent reduction of ABL1 and BCR-ABL1 and in decreased proliferation of tumour cells. "Our results suggest that miR-203 functions as a tumour suppressor and re-expression of this microRNA might have therapeutic benefits in specific hematopoietic malignancies, including some acute or chronic leukaemia’s," concludes Dr. Malumbres. "This may be particularly beneficial for patients who are resistant to small molecule kinase inhibitors like Gleevec as resistant isoforms of ABL and BCR-ABL should contain the target site for miR-203 and are likely to respond to restored miR-203 function." Reference: Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression María J. Bueno, Ignacio Pérez de Castro, Marta Gómez de Cedrón, Javier Santos, George A. Calin, Juan C. Cigudosa, Carlo M. Croce, José Fernández-Piqueras, and Marcos Malumbres Cancer Cell, Vol 13, 496-506, 10 June 2008 ......... ZenMaster


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