Androgen Receptor-Activated Enhancers Simultaneously Regulate Oncogene TMPRSS2 and lncRNA PRCAT38 in Prostate Cancer

Abstract

Prostate cancer is a common carcinoma in males, the development of which involves the androgen receptor (AR) as a key regulator. AR transactivation induces the high expression of androgen-regulated genes, including transmembrane protease serine 2 (<i>TMPRSS2</i>) and long noncoding RNA prostate cancer-associated transcript 38 (<i>PRCAT38</i>). <i>PRCAT38</i> and <i>TMPRSS2</i> are both located on chromosome 21, separated by a series of enhancers. <i>PRCAT38</i> is a prostate-specific long noncoding RNA that is highly expressed in cancer tissue as compared to normal tissue. Here, we show chromatin looping by enhancers E1 and E2 with the promoters for <i>PRCAT38</i> and <i>TMPRSS2</i>, indicating the co-regulation of <i>PRCAT38</i> and <i>TMPRSS2</i> by the same enhancers. The knockout of enhancer E1 or E2 simultaneously impaired the transcription of <i>PRCAT38</i> and <i>TMPRSS2</i> and inhibited cell growth and migration. Moreover, the loop formation and enhancer activity were mediated by AR/FOXA1 binding and the activity of acetyltransferase p300. Our findings demonstrate the utilization of shared enhancers in the joint regulation of two oncogenes in prostate cancer cells.