The androgen receptor gene AR encodes several noncoding RNA transcripts in addition to the androgen receptor, a major regulator of prostate cancer growth. While these noncoding RNAs are not translated into protein products, the RNAs themselves can act to influence the transcription and/or activity of the AR much as other noncoding RNAs have been shown to alter the expression of protein-coding genes. Our overall goal is to gain a complete molecular understanding of the structure and regulation of the novel androgen receptor-associated transcripts (ARat) in order to learn how they function in relation to the AR in prostate cancer.
The specific aims are designed to: 1) complete the molecular characterization of the various ARat transcripts on the human X chromosome. This will require us to: determine the size, sequence and number of ARat RNA transcripts, and determine if there are any open reading frames in the ARat; ascertain whether each ARars orientation is sense or antisense to AR; characterize the promoter region and chromatin structure for each ARat; and use comparative genomics to determine the conserved and presumably essential features of each ARat; 2) characterize and quantify ARat gene expression in various human tissues; 3) determine the physiologic regulation of ARat in prostate cancer cells in vitro as regulated by androgens, other steroid hormones, IGF-I and IGF-II, and other growth factors; and 4) determine the function of each ARat transcript by the method of gene knock-down using RNA interference. These newly discovered ARat ncRNAs represent an entirely novel group of AR-associated products, and they may provide new targets for the treatment of prostate cancer.
| Ling, Jian Qun; Li, Tao; Hu, Ji Fan et al. (2006) CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1. Science 312:269-72 |
