Cell & Neurobiology
Keck School of Medicine
- Cancer Cell Biology
Research OverviewDifferentially expressed genes in prostate cancer and modulation of gene function by intronic microRNA (miRNA)
Our lab�s research has focused on differentially expressed genes in prostate cancer and RNAi-mediated gene expression. We have made advances on four fronts. First, by studying gene profiling in cell-specific, full-length cDNA libraries from prostate cells of various stages by laser capture microdissection, we identified differentially expressed genes as determined by microarray technologies, subtractive hybridization, and Northern blot analyses. Second, we obtained evidence to implicate overexpresseion of several genes in prostate cancer, particularly in androgen-independent prostate cancer. Third, we have demonstrated that the genes identified with the prostatic cancer cell-specific, full-length cDNA libraries using subtractive hybridization and microarray technology reveal intracellular molecular genetic heterogeneity in prostate cancer. Fourth, to elucidate the physiological significance of the identified overexpressed genes, we have developed a cell-specific, polymerase Type II (Pol II)-mediated RNA interference (RNAi) cassette system, using microRNA (miRNA).
About 97% of the human genome is the non-coding DNA; some are microRNAs responsible for RNA-mediated gene silencing through RNA interference (RNAi)-like pathways. We are interested in miRNA because it is a small single-stranded regulatory RNA capable of interfering with intracellular mRNAs. We have focused on the intronic miRNA, which requires type II RNA polymerases (Pol-II) and spliceosomal components for its biogenesis. We are able to induce RNA interference, using the intronic miRNA, in human and murine cells, zebrafish, chicken embryos and adult mice. Our research aims at providing a unique animal model for functional genes related to human diseases and disorders such as Alzheimer�s disease, Parkinson�s disease, Huntington disease, cancer, inflammation, and substance/drug abuse in vivo.
Legend to figure: Mechanism of intronic miRNA biogenesis and gene silencing. The intronic miRNA is generated as parts of precursor messenger RNA (pre-mRNA), which contains protein-coding exons and non-coding introns. The introns are spliced out of the pre-mRNA and further excised into small miRNA molecules which are capable of inducing RNA interference (RNAi), while the exons are ligated to form a mature mRNA for protein translation.