miRIDIAN® microRNA Mimics Help Researchers Make Strides in Cancer Biology

Jon Karpilow, Ph.D.

Work by a group at the National Institute of Health (Raveche, Salerno et al. 2007) recently demonstrated the power of Dharmacon miRIDIAN® microRNA Mimics. miRIDIAN microRNA Mimics and Inhibitors are highly efficient modulators of miRNA activity for use in miRNA functional studies. Complete collections of advanced-design miRIDIAN microRNA Mimics and Inhibitors are available for all human, mouse & rat microRNAs in Sanger miRBase 9.0.

In an investigation designed to identify the molecular origins of a common B-cell leukemia (B-cell chronic lymphocytic leukemia, CLL), the authors initiated their studies by identifying the chromosomal position of the gene in a mouse model (NZB mice) that exhibited phenotypic characteristics similar to human CLL patients (e.g., late stage development of a monoclonal lymphoproliferation).

Extensive genetic mapping based on microsatellite and simple sequence length polymorphisms (SSLP) identified three separate loci on chromosomes 14, 18, and 19 that could be linked to the murine lymphoproliferative disease (LPD). Of particular interest was the site identified on chromosome 14. Detailed analysis showed that the genes in this region exhibited synteny with those found on human chromosome position 13q14, a site frequently associated with genetic mutations in patients with CLL. Subsequent DNA sequence analysis identified a unique point mutation in the 3’ flanking region of the precursor miRNA16-1 (pre-miR16-1).

Previous studies had identified abnormal microRNA signatures associated with CLL patients. Likewise, when the investigators examined miR-16 levels in both primary tissues and cell lines derived from NZB mice, expression of this miRNA was found to be down-regulated when compared to samples taken from control tissues. Subsequent reconstitution studies utilizing miR16-1 miRIDIAN microRNA Mimic found that supplementing cells with this single miRNA led to a shift of cells away from S-phase and an increase in apoptosis.

Overall, the murine studies strongly support findings made in human CLL patients and identify NZB mice as a model system for future investigations of B-cell chronic lymphocytic leukemia. In addition, the identification of miR16-1 as a potential trigger for LPD adds to the growing evidence that small noncoding RNAs play a critical role in oncogenesis. Future applications of Dharmacon miRIDIAN microRNA products, both the specificity-enhanced Mimics and the highly potent Inhibitors, promise to broaden our understanding of the contributions these molecules make to cellular physiology and open doors to novel therapeutic strategies for cancer treatment.

Raveche, E. S., E. Salerno, et al. (2007). "Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice." Blood. Prepublished online March 9, 2007