Nuclear receptor (NR)-mediated transcription is a dynamic process that is regulated by the binding of distinct ligands that induce conformational changes in the NR. These molecular alterations lead to the recruitment of unique cofactors (coactivators or corepressors) that control the expression of NR-regulated genes. Here, we show that a stretch of proline residues located within the N-terminus of AR is necessary for maximal androgen-mediated prostate cancer cell growth and migration. Furthermore, this polyproline domain is necessary for the expression of a subset of AR-target genes, but is dispensable for classical AR-mediated gene transcription. Using T7 phage display, we subsequently identified a novel AR-interacting protein, SH3YL1, whose interaction with AR is dependent upon this polyproline domain. Like the AR polyproline domain, SH3YL1 was required for maximal androgen-mediated cell growth and migration. Microarray analysis revealed that SH3YL1 also regulated a subset of AR-modulated genes. Correspondingly, we identified ubinuclein1 (UBN1), a key member of a histone H3.3 chaperone complex, as a transcriptional target of AR/SH3YL1. Moreover, UBN1 was necessary for maximal androgen-mediated proliferation and migration. Collectively, our data link a specific surface located within ARs N-terminus to the recruitment of a novel cofactor, SH3YL1, which is required for the androgen-mediated expression of UBN1. Importantly, this signaling network was important for both androgen-mediated prostate cancer cell growth and migration. This work is significant because it could aid in the development of selective androgen receptor modulators (SARMs) and have therapeutic implications for AR-driven diseases.
Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus.
Specimen part
View SamplesIn this study, we used RNA-seq to investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in 10 paired tumor and normal pancreatic samples from patients Overall design: 10 paired tumor and normal pancreatic samples from patients
Network-based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer.
Specimen part, Subject
View SamplesThis study compared the gene expression change of glioblastoma stem-like cells before and after retinoic acid treatment
Regulation of glioblastoma stem cells by retinoic acid: role for Notch pathway inhibition.
Specimen part, Cell line, Treatment
View SamplesPurpose: Investigate effects of high salt on human macrophage activation Methods: Human monocytes-derived macrophages were treated by additional 51mM NaCl for 24 hours (NaCl groups) or not (Control groups). mRNA profiles were generated by RNA-Seq, in triplicate, using Ion proton(Life tech). qRT–PCR validation was performed using SYBR Green assays. Results: High salt significantly promotes pro-inflammatory gene expressions,while suppresses the expressions of anti-inflammatory genes and pro-endocytic genes in human macrophages. Conclusions: Our results identify a novel macrophage activation state, M(Na), and high salt as a potential environmental risk factor for lung inflammation through the induction of M(Na) Overall design: Human monocytes-derived macrophages were treated by additional 51mM NaCl for 24 hours (NaCl groups) or not (Control groups). mRNA profiles were generated by RNA-Seq, in triplicate, using Ion proton(Life tech). qRT–PCR validation was performed using SYBR Green assays.
High salt primes a specific activation state of macrophages, M(Na).
No sample metadata fields
View SamplesLike most adult stem cells, culturing and expansion of satellite cells (muscle stem cells) are difficult, that prevents the utilization of satellite cells in cell-based therapies. Here, we reveal that T cells infiltrated into the injury site upon acute inflammation are able to promote muscle stem cell proliferation, expansion, and maintain their injury reparation abilities in vivo. Four cytokines, IL-1a, IL-13, TNF-a, and IFN-?, were identified as the effective components secreted by T cells to faciliate satellite cell propagation Overall design: Comparison of mRNA expression profile of satellite cells between different treatment in different sample
Combination of inflammation-related cytokines promotes long-term muscle stem cell expansion.
No sample metadata fields
View SamplesWe generated induced human hepatocyte by transduction of several lineage specific transcription factors and analyzed the gene expression profile of generated hepatocytes and freshly isolated human hepatocytes through RNA sequencing. Overall design: Global gene expression profile analysis
Human hepatocytes with drug metabolic function induced from fibroblasts by lineage reprogramming.
No sample metadata fields
View SamplesFibroblast growth factor 21 (Fgf21) is a liver-derived, fasting-induced hormone with broad effects on growth, nutrient metabolism and insulin sensitivity. Here, we report the discovery of a novel mechanism regulating Fgf21 expression under growth and fasting-feeding. The Sel1LHrd1 complex is the most conserved branch of mammalian endoplasmic reticulum (ER)- associated degradation (ERAD) machinery. Mice with liver-specific deletion of Sel1L exhibit growth retardation with markedly elevated circulating Fgf21, reaching levels close to those in Fgf21 transgenic mice or pharmacological models. Mechanistically, we show that the Sel1LHrd1 ERAD complex controls Fgf21 transcription by regulating the ubiquitination and turnover (and thus nuclear abundance) of ER-resident transcription factor Crebh, while having no effect on the other well-known Fgf21 transcription factor Ppar. Our data reveal a physiologically regulated, inverse correlation between Sel1L-Hrd1 ERAD and Crebh-Fgf21 levels under fasting-feeding and growth. This study not only establishes the importance of Sel1L-Hrd1 ERAD in the liver in the regulation of systemic energy metabolism, but also reveals a novel hepatic ERADCrebh- Fgf21 axis directly linking ER protein turnover to gene transcription and systemic metabolic regulation.
Hepatic Sel1L-Hrd1 ER-associated degradation (ERAD) manages FGF21 levels and systemic metabolism via CREBH.
Specimen part
View SamplesGGPPS was the key enzyme of mevalonate metabolic pathway which was used to synthesize the geranylgeranyl pyrophosphate (GGPP). When we deletion the GGPPS in the sertoli cell and the germ cell loss were found .
Altered protein prenylation in Sertoli cells is associated with adult infertility resulting from childhood mumps infection.
Age, Specimen part
View SamplesWe have developed mouse models for serous epithelial ovarian cancer (SEOC) based on conditional inactivation of p53 and Rb tumor suppression (RB-TS) in combination with or without Brca1/2 following injection of adenovirus expressing Cre recombinase into the ovarian bursa. These models develop metastatic (Stage IV) disease with key histopathological features resembling human SEOC.To determine whether these mouse tumors resemble human SEOC at the molecular level, we conducted global gene expression analysis on 27 ovarian carcinomas and 3 pooled normal ovarian surface epithelium samples (single epithelial layer isolated from ovarian surface by laser capture).
Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer.
Specimen part
View SamplesIt is still unclear that how obesity increases the risk of breast cancer. To address this question, we used mRNA microarrays to characterize mouse breast tumor EO771 cells treated with mouse recombinant A-FABP protein and compared the data from their controls.
Circulating Adipose Fatty Acid Binding Protein Is a New Link Underlying Obesity-Associated Breast/Mammary Tumor Development.
Cell line
View Samples