Project description:The goals of this study were to evaluate changes in microRNA expression following androgen treatment. Four treatment groups were studied: untreated and those treated with 0.1, 1.0, and 10.0 nM of synthetic androgen (R1881). Data is relative to the untreated sample.
Project description:The goals of this study were to evaluate changes in microRNA expression following androgen treatment. Four treatment groups were studied: untreated and those treated with 0.1, 1.0, and 10.0 nM of synthetic androgen (R1881). Data is relative to the untreated sample.
Project description:This SuperSeries is composed of the following subset Series: GSE16212: Androgen repsonsive microRNAs in LNCaP cell Lines GSE16213: Androgen repsonsive microRNAs in LAPC-4 cell lines Refer to individual Series
Project description:Although decades of research have established that androgen is essential for spermatogenesis, androgen’s mechanism of action remains elusive. This is in part because only a few androgen-responsive genes have been definitively identified in the testis. Here, we report that microRNAs—small, noncoding RNAs—are one class of androgen-regulated trans-acting factors in the testis. Specifically, by using androgen suppression and androgen replacement in mice, we show that androgen regulates the expression of several microRNAs in Sertoli cells. Our results reveal that several of these microRNAs are preferentially expressed in the testis and regulate genes that are highly expressed in Sertoli cells. Because androgen receptor–mediated signaling is essential for the pre- and postmeiotic germ cell development, we propose that androgen controls these events by regulating Sertoli/germ cell–specific gene expression in a microRNA-dependent manner.
Project description:Although decades of research have established that androgen is essential for spermatogenesis, androgen’s mechanism of action remains elusive. This is in part because only a few androgen-responsive genes have been definitively identified in the testis. Here, we report that microRNAs—small, noncoding RNAs—are one class of androgen-regulated trans-acting factors in the testis. Specifically, by using androgen suppression and androgen replacement in mice, we show that androgen regulates the expression of several microRNAs in Sertoli cells. Our results reveal that several of these microRNAs are preferentially expressed in the testis and regulate genes that are highly expressed in Sertoli cells. Because androgen receptor–mediated signaling is essential for the pre- and postmeiotic germ cell development, we propose that androgen controls these events by regulating Sertoli/germ cell–specific gene expression in a microRNA-dependent manner. Control, Treated, Rescued (3 groups)
Project description:RNA-Seq analysis of prostate cancer cell line LNCaP treated with vehicle (C), androgen (R), androgen and IMTPPE (R + IMTPPE), androgen and JJ-(+)-450 (androgen + (-)450), androgen and JJ-(-)450 (androgen + (-)450), androgen and enzalutamide (androgen +Enz). To evaluate if our compounds can inhibit AR function specifically and completely, LNCaP mRNA profiles of cells treated with IMTPPE, (+)-JJ-450 and (-)-JJ-450, comparing to enzalutamide. RNA isolation was performed using RNeasy Mini kit (Qiagen), RNA Sequencing was carried out by Genomics Research Core of University of Pittsburgh using Illumina NextSeq 500 system. The sequence reads that passed FASTQC were analyzed at the transcript level. Each sample was mapped to the Human Ensembl reference genome GRCh38. We definied different expression genes with a fold change ≥2.0 and FDR <0.05. Both (-)-JJ-450 and enzalutamide are very specific to AR, with 56 and 186 DE genes comparing to control samples respectively. IMTPPE and (+)-JJ-450 can inhibit most of the androgen responsive genes, but also some other genes were affected. (-)-JJ-450 is a novel compound inhibts AR function specifically and completely, and it is a potential lead compound for the treatment of CRPC, including those resistant to enzalutamide.
Project description:Orthotopic tumors were previously generated from parental Prostate Luminal (PLum) cells under androgen‑dependent (PLum-AD) and androgen‑independent (PLum-AI) conditions in order to establish cellular models of prostate cancer progression (Abou-Kheir et al., 2011; doi: 10.1371/journal.pone.0026112). We used microarrays to evaluate the differential gene expression profiles underlying progression of prostate cancer from primary androgen-dependent stage to advanced androgen-independent stage using newly isolated murine prostate cancer cell lines. Those cell lines represent novel in vitro models of androgen‑dependent and –independent prostate cancer, recapitulating the progression of the disease to a more invasive phenotype upon androgen deprivation.
Project description:To study androgen receptor transcriptomic activation in the presence of androgen in bladder cancer cell lines. A uniquely derived AR expressing clone of the bladder cancer cell line UMUC3 was derived and validated prior to ChIP-seq experiments. Androgen receptor chromatin immunoprecipitation (AR ChIP-seq) was used to determine the overall expression changes in repsonse to treatment with synthetic androgen. Evaluation of genes associated with androgen receptor stimulation were used for focused analysis when combined with microarray data.