Abstract

Natural Killer cells play a vital role in the control of cancer and microbial infections. One of the mechanisms by which these cells act is through the production of interferon (IFN)-gamma in response to many extracellular signals. These extracellular signals have effects on transcriptional and post transcriptional regulation of IFN-gamma gene expression. MicroRNAs may be one of the important agents involved in post-transcriptional regulation of IFN-gamma gene expression. Furthermore, through bioinformatic analysis, putative miRNAs that might target IFN-gamma gene for gene regulation have been identified. Using miRNA arrays, we have screened for the expression of miRNAs in NK-92 cells stimulated for 4h with IL (interleukin) -2, IL-12, IL-15, IL-18, IL-21, IFN-alpha, PMA and a combination of IL-12 and PMA. Our studies by miRNA profiling indicate that miR29a, miR27 and miR181, through bioinformatics are known to target IFN-gamma, are modulated by signals that up-regulate IFN-gamma mRNA. This data forms a base-line to further study the role of microRNAs in NK cell biology. These studies will utilize lentiviruses to overexpress specific microRNAs or disrupt the miRNA pathway in order to elucidate the role of miRNAs in NK cell gene expression.

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