HuR promotes castration-resistant prostate cancer progression by altering ERK5 activation via posttranscriptional regulation of BCAT1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE254851 | GEO | 2024/02/05
REPOSITORIES: GEO
Similar Datasets
Project description:HuR promotes castration-resistant prostate cancer progression by altering ERK5 activation via posttranscriptional regulation of BCAT1
| PRJNA1072083 | ENA
Project description:HuR stimulates the activity of intestinal stem cells by enhancing Paneth cell function via activation of mitochondrial metabolism, thus promoting renewal of the intestinal mucosa
2023-09-08 | GSE242410 | GEO
Project description:ionPurpose: The goal of this study is to investigate how HuR regulates NASH progression. Methods: The hepatic mRNA profiles of HuR flox/flox and hepatocyte-specific HuR knockout (HKO) mice (n=3 for each group) fed with an MCD for 3 weeks were generated by deep sequencing using an Illumina Novaseq platform. Paired-end clean reads were aligned to the mouse reference genome(Ensemble_GRCm38.p6) with TopHat (version 2.0.12), and the aligned reads were used to quantify mRNA expression by using HTSeq-count (version 0.6.1). Conclusion: Our study represents the first detailed analysis of hepatic mRNA profiles in HuR flox/flox and hepatocyte-specific HuR knockout (HKO) mice fed with an MCD for 3 weeks, generated by RNA-seq technology. Our results show that 353 genes were upregulated and 422 genes were downregulated. Gene Ontology (GO) analysis showed that genes related to leukocyte migration, leukocyte chemotaxis, cell chemotaxis, neutrophil migration and Fc receptor signaling pathway were significantly decreased, which contributes to the protective effects of NASH progression in HKO mice.
2023-06-17 | GSE152670 | GEO
Project description:Analysis of RNA immunoprecipitation of HuR, a RNA binding protein (RBP), in breast cancer cell lines. This approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich (ARE) regions of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR associated mRNAs found individually or in both cell types. Two novel HuR targets, CD-9 and CALM-2, were identified and validated by quantitative RT-PCR and biotin pulldown analysis. Our findings reveal that the differential regulation of these two cancer-related genes by HuR was contingent upon the cellular environment. RNA immunoprecipitation of the HuR RNA binding protein by 3A2 antibody and IgG (control) from two human breast cancer cell lines, MCF-7 and MDA-MB-231 .
2010-06-24 | E-GEOD-17820 | biostudies-arrayexpress
Project description:Castration-resistant prostate cancer (CRPC) that arise after the failure of androgen deprivation therapy is a leading cause of deaths in prostate cancer patients.However, its underlying mechanism is not fully understood. Long noncoding RNAs (lncRNAs) act as crucial regulators in a lot of human cancers, yet their potential roles and molecular mechanisms in CRPC are poorly understood.The goal of this study is to identify the differentially expressed lncRNAs in LNCaP cells and its two castration resistant sublines. Our study reveals that deregulation of lncRNAs is involved in the initiation and progression of CRPC.
2017-08-18 | GSE93929 | GEO
Project description:NAFLD has become the most common chronic liver disease worldwide. Human antigen R (HuR), an RNA-binding protein, is an important post-transcriptional regulator. HuR has been reported as a key player in regulating lipid homeostasis in the liver and adipose tissues by using tissue-specific HuR knockout mice. However, the underlying mechanism by which hepatocyte-specific HuR regulates hepatic lipid metabolism under metabolic stress remains unclear and is the focus of this study.
2022-12-01 | GSE213215 | GEO
Project description:Integrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability In this dataset, we employed two distinct experiments. 1) HuR RIP-chip to identify mRNA targets of HuR. 2) HuR knockdown to identify mRNAs whose expression are dependent on HuR. All 12 samples were normalized with PLIER using Affymetrix power tools. To identify RNA targets of HuR, HuR RIP samples were compared to Mock RIP samples. To identify RNA regulated by HuR, HuR knockdown samples were compared to mock knockdown samples.
2011-08-18 | E-GEOD-29778 | biostudies-arrayexpress
Project description:RNA binding proteins (RBPs) regulate gene expression through several post-transcriptional mechanisms. The broadly expressed HuR/ELAVL1 RBP is important for proper function of multiple cell types in the immune system, and has been proposed to positively control the expression of cytokine and other mRNAs upon activation by regulating their 3′ UTRs. However, this mechanism has not been previously dissected in stable cellular settings. In this study, HuR demonstrated strong anti-apoptotic and activation roles in the Jurkat T cell line. Detailed transcriptomic analysis of HuR knockout cells revealed a substantial negative impact on the activation program, coordinately preventing the expression of several gene categories related to the immune response, including all cytokines. Measurements of IL-2 production showed a significant defect in knockout cells, which was rescued upon reintroduction of HuR. Interestingly, the mechanism of HuR regulation did not involve control of the cytokine 3′ UTRs: HuR knockout did not affect the activity of several cytokine 3′ UTR reporters in 293 cells. Similarly, HuR had no effect on the regulation of IL-2 and TNF 3′ UTRs in resting or activated Jurkat cells. Instead, impaired cytokine production corresponded with defective induction of the IL-2 promoter upon activation. Accordingly, upregulation of the master transcription factor NFATC1 upon activation was also impaired in HuR KOs, without effects on its 3′ UTR. Together, these results indicate that HuR controls cytokine production through coordinated upstream pathways, and that additional mechanisms must be considered in investigating its function.
2019-06-05 | GSE121966 | GEO
Project description:Comprehensive meta-analysis and target screening confirmed that the mRNA-binding protein of ELAV-family HuR is oncogenic and universally upregulated in brain tumors, which highlight HuR as an universal chemotherapeutic target. HuR functionality in cancer cells is strictly dependent on HuR nuclear/cytoplasmic shuttling and dimerization; therefore, we developed a new class of inhibitors of HuR protein dimerization by utilizing medicinal chemistry techniques and reporter cell-based assay of HuR dimerization. The therapeutic potentials of lead compound (SRI-42127) were evaluated in five primary patient-derived glioma xenolines of classic, proneural, and mesenchymal subtypes, in vitro, and in mouse glioma model, in vivo. The Illumina global RNA-Sequencing was performed on PDGx-derived glioma neurospheres of different subtypes after treatment with DMSO (control) or SRI-42127 (3 uM) for 12 h to analysis transcripts and cell-signaling pathways affected by new inhibitor of HuR dimerization.
2020-11-05 | GSE158271 | GEO
Project description:Although RNA-binding proteins (RBPs) coordinate many key decisions during cell growth and differentiation, the dynamics of RNA–RBP interactions have not been extensively studied on a global basis. We immunoprecipitated endogenous ribonucleoprotein complexes containing HuR and PABP throughout a T-cell activation time course and identified the associated mRNA populations using microarrays. We used Gaussian mixture modeling as a discriminative model, treating RBP association as a discrete variable (target or not target), and as a generative model, treating RBP-association as a continuous variable (probability of association). We report that HuR interacts with different populations of mRNAs during T-cell activation. These populations encode functionally related proteins that are members of the Wnt pathway and proteins mediating T-cell receptor signaling pathways. Moreover, the mRNA targets of HuR were found to overlap with the targets of other posttranscriptional regulatory factors, indicating combinatorial interdependence of posttranscriptional regulatory networks and modules after activation. Applying HuR mRNA dynamics as a quantitative phenotype in the drug-gene-phenotype Connectivity Map, we identified candidate small molecule effectors of HuR and T-cell activation. We show that one of these candidates, resveratrol, exerts T-cell activation-dependent posttranscriptional effects that are rescued by HuR. Thus, we describe a strategy to systematically link an RBP and condition-specific posttranscriptional effects to small molecule drugs. Keywords: Timecourse, RIP, Immunoprecipitation, HuR, ELAVL1, PABP, T cell activation Timecourse experiment: 0hr, 4hr, and 12hr post-activation of Jurkat cells. Four samples collected: HuR-IP, PABP-IP, Neg-IP and Total RNA. 3 Biological replicates per condition and sample that were independently grown and harvested.
2009-08-19 | E-GEOD-11989 | biostudies-arrayexpress