MicroRNAs (miRs) have recently been found to be important regulatory agents in cancers. More specifically, the miR-17-92 cluster, which is... Show moreMicroRNAs (miRs) have recently been found to be important regulatory agents in cancers. More specifically, the miR-17-92 cluster, which is overexpressed in acute leukemias with fusions of the mixed lineage leukemia (MLL) gene, such as MLL-AF9 and MLL-ELL, has been shown to affect regulation of normal genes in human acute leukemias. Studies show that the miR-17-92 cluster targets genes in acute leukemias that play roles in cell differentiation and proliferation. To study this, a luciferase reporter assay was performed showing that miR-17-92 targets transforming growth factor beta induced (TGF!I) and suppressor of zeste 12 (SUZ12). Studies have shown TGF!I to be downregulated in MLL fusion acute leukemias and SUZ12 to have an inverse correlation of expression with miR-17-92. Both genes are important in the regulation of cell differentiation and proliferation. Furthermore, previous studies have shown that the miR- 17-92 cluster partially blocks cell differentiation and induces cell proliferation, and when combined with MLL fusions, these effects are amplified. To further validate the results of these studies, a colony forming assay was performed confirming that a knock-in version of the miR-17-92 cluster promotes formation of colonies of non-differentiating cells, especially in the presence of MLL-AF9 and MLL-ELL. These studies implicate the miR- 17-92 cluster as an important regulator in acute leukemias with MLL fusions given its effect on cell differentiation and proliferation. M.S. in Biology, May 2011 Show less
