Reexpression of Lost MicroRNA May Inhibit Tumor Growth

They suggest that a therapeutic treatment aimed at reexpression of this miRNA could be beneficial.

MicroRNAs are small non-coding bits of RNA that can modulate the expression of specific target genes. Investigators at the Spanish National Cancer Research Center (Madrid) reported in the June 2008 issue of the journal Cancer Cell that they had 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 investigators employed miRNA expression profiling techniques to reveal that one particular miRNA, miR-203, was silenced by both genetic and epigenetic mechanisms in several mouse and human blood cell malignancies, including chronic myelogenous leukemias and certain acute lymphoblastic leukemias. Transcriptional silencing of miR-203 caused upregulation of the oncogene ABL1 and the BCR-ABL1 oncogenic fusion protein. On the other hand, restoration of miR-203 resulted in reduction of ABL1 and BCR-ABL1 and in decreased proliferation of tumor cells.

"Our results suggest that miR-203 functions as a tumor suppressor, and re-expression of this microRNA might have therapeutic benefits in specific hematopoietic malignancies, including some acute or chronic leukemias,” said senior author Dr. Marcos Malumbres, a senior researcher at the Spanish National Cancer Research Center. "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.”


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Spanish National Cancer Research Center