RNA-seq of human myoblasts where AR isoform 2 was either knocked-down or upregulated.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136807 | GEO | 2021/06/28
REPOSITORIES: GEO
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Project description:RNA-seq of human myoblasts where AR isoform 2 was either knocked-down or upregulated.
| PRJNA563704 | ENA
Project description:Together with the Estrogen, Progesterone, and Glucocorticoid Receptors, the Androgen Receptor (AR) is a member of the type I nuclear receptor superfamily, a class of transcription factors that are activated by steroid hormones1. Nuclear receptors share a common three-domain structure, comprising a highly variable amino-terminal domain (NTD), with potent transcriptional activator capability, a central two zinc finger motifs DNA-binding domain (DBD), and a well-conserved carboxy-terminal ligand-binding domain (LBD) responsible for interacting with the transcriptional machinery1. Given their modular structure, expression of isoforms resulting from alternative splicing or starting and termination events have profound effects on nuclear receptor activity and function. Several AR variants (AR-Vs) have been identified from prostate cancer clinical specimens, arising from multiple mechanisms, including genomic rearrangements2 and upregulation of splicing factors3. This seminal discovery has provided the molecular basis for a deeper understanding of AR-related diseases, with potential to be translated in identification of novel therapeutic targets and promising prognostic markers4–6. By deeply sequencing the transcriptome of human brains, here we identified AR-2 as the most expressed AR isoform. Furthermore, we found that AR-2 is widely expressed in other human tissues, forms heterodimers with the full length AR and acts as a repressor of its transcriptional activity. Delivery of this isoform via adeno-associated virus (AAV9) resulted in significant amelioration of the disease phenotype in a mouse model of spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease with unmet clinical need caused by a toxic gain of function of polyglutamine-expanded (polyQ) AR7. Collectively, these results establish a physiological role of AR-2 in fine-tuning full length AR activity and demonstrate the feasibility and therapeutic benefit of modulating this variant for treating SBMA and other AR-related diseases.
2021-06-29 | GSE138053 | GEO
Project description:Effect of AR isoform and total AR depletion and AR-v19 oeverexpression in UM-UC-3 bladder cancer cells
| PRJNA858017 | ENA
Project description:To investigate AR regulated transcription, full length, AR-v19 splice variant or total AR was siRNA depleted or AR-V19 was overexpressed in UM-UC-3 cells.
2023-01-05 | GSE208018 | GEO
Project description:AR isoform 2 is widely expressed in human tissues and acts as a decoy receptor to regulate AR transcriptional activity
| PRJNA574351 | ENA
Project description:Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive prostate cell lines, LNCaP-C42B4 and CWR22Rv1, knockdown of AR expression showed a more pronounced effect on AR-induced transcription and cell growth than androgen depletion. Using cDNA microarrays, we also compared the transcriptional profiles induced by either androgen depletion or AR knockdown. Although a significant number of transcripts appear to be regulated by both androgen depletion and AR knockdown, we observed a subset of transcripts affected only by androgen depletion but not by AR knockdown, and vice versa. Finally, we demonstrated a direct role for AR in promoting tumor formation and growth in a xenograft model. Taken together, our results elucidate an important role for the AR in androgen-insensitive prostate cancer cells, and suggest that AR can be used as a therapeutic target for androgen-insensitive prostate cancers.
2007-05-04 | E-SMDB-4028 | biostudies-arrayexpress
Project description:To understand the effects of the transient ablation of BRCA2 gene expression in dividing human breast cells, we transiently knocked down BRCA2 mRNA in HMEC and other cells. Microarray analysis of mRNAs revealed the down-regulation of the mRNAs of ubiquitin cross-reacting protein (UCRP) and the E2 enzyme that help conjugating UCRP to its target proteins, namely UBE2L6 (UbcH8), in BRCA2 ablated cells. UCRP is an interferon regulated protein, involved in cell growth and cell cycle events by participating in the degradation/modulation of cell cycle regulatory proteins. Quantitative-PCR and Northern analysis confirmed down-regulation of UCRP and UBE2L6 with BRCA2 knockdown, respectively. Since UCRP and UCRPylation have critical roles in the innate immunity against viral infection and during pregnancy, our observation may indicate new roles of the BRCA2 protein.
| S-EPMC3085986 | biostudies-literature
Project description:We previously encountered regulatory processes where dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone-related protein (PTHrP) gene repression through the estrogen receptor (ER)M-NM-1, but not the androgen receptor (AR) in breast cancer MCF-7 cells. Here, we investigated whether such an aberrant ligand-nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed a functional AR and at negligible levels of ERM-NM-1, and progesterone receptors. Both suppression of PTHrP and activation of the PSA genes were observed after treatment of E2, DHT and R5020. Consistent with the previous notion that the AR in LNCaP cells lost the ligand specificity due to a mutation AR (Thr-Ala877), our study using siRNA targeting each NR revealed that the AR, but not the other NRs, monopolized the role as the mediator of shared hormone-dependent regulation. These results were invariably associated with nuclear translocation of this mutant AR. Microarray of the genes regulated by either DHT, E2 or R5020 downstream of the AR (Thr-Ala877) revealed that more than half genes overlapped in LNCaP cells. Noticeably, AR (wild-type, wt) and AR (Thr-Ala877) were equally responsible for the E2-AR interactions. Fluorescent microscopic experiments demonstrated that both EGFP-AR (wt) and EGFP-AR (Thr-Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Further, a promoter assay revealed that breast cancer MCF-7 and Rv22 cells also exhibited such an aberrant E2-AR (wt) signaling. We postulate entangled interactions between the AR (wt) and E2 in a certain hormone-sensitive cancer cells. Total RNAs from the LNCaP cells transfected with control siRNA (siCT) or siRNA for AR (siAR) transfected LNCaP cells before 24 hr followed by exposed to 10-7M of DHT, E2 or R5020 exposure for another 24 h, respectively, were used.
2014-06-19 | E-GEOD-58615 | biostudies-arrayexpress
Project description:Angiogenesis is a very complex physiological process, which involves multiple pathways that are dependent on the homeostatic balance between the growth factors (stimulators and inhibitors). This tightly controlled process is stimulated by angiogenic factors, which are present within the tumor and surrounding tumor-associated stromal cells. The dependence of tumor propagation, invasion and metastasis on angiogenesis makes the inhibitors of new blood vessel formation attractive drugs for treating the malignancies. Angiogenesis can be disrupted by several distinct mechanisms: by inhibiting endothelial cells, by interrupting the signaling pathways or by inhibiting other activators of angiogenesis. This strategy has shown therapeutic benefit in several types of solid tumors, leading to Food and Drug Administration (FDA) approval of anti-angiogenic agents in the treatment of kidney, non-small cell lung, colon and brain cancers. Although no angiogenesis inhibitors have been approved for patients with metastatic prostate cancer, therapies that target new blood vessel formation are still an emerging and promising area of prostate cancer research.
| S-EPMC4023362 | biostudies-literature
Project description:We previously encountered regulatory processes where dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone-related protein (PTHrP) gene repression through the estrogen receptor (ER)α, but not the androgen receptor (AR) in breast cancer MCF-7 cells. Here, we investigated whether such an aberrant ligand-nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed a functional AR and at negligible levels of ERα, and progesterone receptors. Both suppression of PTHrP and activation of the PSA genes were observed after treatment of E2, DHT and R5020. Consistent with the previous notion that the AR in LNCaP cells lost the ligand specificity due to a mutation AR (Thr-Ala877), our study using siRNA targeting each NR revealed that the AR, but not the other NRs, monopolized the role as the mediator of shared hormone-dependent regulation. These results were invariably associated with nuclear translocation of this mutant AR. Microarray of the genes regulated by either DHT, E2 or R5020 downstream of the AR (Thr-Ala877) revealed that more than half genes overlapped in LNCaP cells. Noticeably, AR (wild-type, wt) and AR (Thr-Ala877) were equally responsible for the E2-AR interactions. Fluorescent microscopic experiments demonstrated that both EGFP-AR (wt) and EGFP-AR (Thr-Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Further, a promoter assay revealed that breast cancer MCF-7 and Rv22 cells also exhibited such an aberrant E2-AR (wt) signaling. We postulate entangled interactions between the AR (wt) and E2 in a certain hormone-sensitive cancer cells.
2014-06-19 | GSE58615 | GEO