( as a drug target ...)RNAi as a Tool for Mammalian Gene Analysis: Applications of siRNAs

as a drug target, Li et al (6) used siRNAs to reduce cyclin E expression in hepatocellular carcinoma (HCC) cells. As expected, the cyclin E siRNA promoted apoptosis of HCC cells and blocked cell proliferation. In addition, the cyclin E siRNA inhibited HCC tumor growth in nude mice demonstrating the potential for creating drugs targeting cyclin E.

Pathway Analysis
Another key application for siRNAs is pathway analysis. Reducing the expression of a single gene has implications on the expression and activities of genes that are in the same pathway(s). For instance, reducing the levels of a transcription factor such as p53 will reduce the expression of any gene that relies on the p53 transcription factor for activity. Furthermore, the expression of genes that are regulated by gene products that are controlled by p53 should likewise be impacted. Treating cells with an siRNA targeting a given gene and then monitoring the expression of other genes using a microarray will make it possible to identify genes that are associated with the target gene. Furthermore, a specific pathway can be dissected by treating cells sequentially with siRNAs targeting the various genes in the pathway and assaying which genes are affected. This will make it possible to assign a position in the pathway for each gene.

* Ramos-Nino et al (7) exposed RPM cells to crocidolite asbestos and monitored gene expression using arrays. Genes were ca
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