The recent discovery of miRNAs (miRs) may bring fundamental and revolutionary changes in understanding and treatment of human diseases. So far 2154 human miRs are discovered. It is believed that most human protein coding genes and the entire spectrum of biological pathways are under the control of miRs, as one miR can regulate hundreds or even thousands of genes. Deregulation of miRs may contribute to various diseases and be used as robust biomarkers for diagnosis, staging, prognosis and the response to therapy. We are interested in the role of miRs in human diseases such as cancer. We are developing an miR profiling method the only RT-qPCR assay that can specifically profile all miRs. We are using this novel technique to screen miR biomarkers for human diseases such as cancer and inflammatory diseases. On the other hand, we are studying miRs' role in immune suppression and immune over-activation/autoimmunity in vivo by knockin and knockout techniques. Four miR transgenic mouse models have been generated, all of which show interesting phenotype related to cancer. The epigenic regulations of these miRs related to HDACs will be explored.