LncRNA-GAS5 negative regulation of YAP-target genes expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE129624 | GEO | 2019/10/29
REPOSITORIES: GEO
Similar Datasets
Project description:LncRNA-GAS5 negative regulation of YAP-target genes expression
| PRJNA532331 | ENA
Project description:Long non-coding RNAs (lncRNAs) are a class of transcribed RNA molecules greater than 200 nucleotides long. Though do not encode proteins, they play functional roles in gene expression regulation. LncRNAs are notably abundant in the brain, however, their neural functions are largely unknown. Here we demonstrate that repeated short- and long-term cocaine administrations all decreased the expression of lncRNA Gas5 in the nucleus accumbens (NAc) of adult male mice. To illustrate the functional role of Gas5, we performed viral mediated overexpression of Gas5 in the NAc and found decreased cocaine-induced conditioned place preference. Furthermore, Gas5 overexpression also led to decreased drug intake, lower motivation, repressed compulsivity to acquire cocaine, and faster extinction of drug during cocaine self-administration. Transcriptome profiling identified numerous Gas5 mediated gene expression changes that are enriched in relevant neural function categories. Interestingly, these Gas5 regulated gene expression changes significantly overlap with chronic cocaine induced transcriptome alterations, which suggests that Gas5 may serve as a main transcription regulator of cocaine response. Our study therefore displays a novel lncRNA based molecular mechanism of cocaine action.
2020-06-26 | GSE146005 | GEO
Project description: Not available
| S-EPMC3792431 | biostudies-other
Project description:To identify RNAs interacting with lncRNA Gas5 in hippocampal neurons, we performed a Gas5 pulldown from mouse hippocampal cultures using a biotinylated Gas5 bait and performed total and small RNA sequencing
2022-11-07 | GSE180503 | GEO
Project description:Microarray analyses with cells/tissues overexpressing YAP have revealed many transcription targets of YAP (Dong et al, 2007; Zhao et al, 2008). However, as YAP induces transformation of non-cancerous cells, we thought many of known targets of YAP may be indirect consequence of transforming property of YAP. To identify the immediate transcription targets for YAP, we utilized immortalized mammary epithelial MCF-10A cells expressing a tamoxifen inducible, hyperactive (S127/381A) YAP mutant (MCF-10A ERT2-YAP 2SA). MCF-10A ERT2 and MCF-10A ERT2-YAP 2SA are generated. Each cell line was treated with 0.1% of ethanol (solvent) or 1uM of 4-hydroxytamoxifen for 2 or 6 hours. This makes 6 samples per set. The experiments were done in duplicate. The expression data from MCF-10A ERT2 and MCF-10A ERT2-YAP 2SA before tamoxifen treatment can serve as control.
2015-11-23 | E-GEOD-60579 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) are recently characterized players that are involved in the regulatory circuitry of self-renewal in human embryonic stem cells (hESCs). However, the specific roles of lncRNAs in this circuitry are poorly understood. Here, we determined that growth-arrest-specific transcript 5 (GAS5), which is a known tumor suppressor and growth arrest gene, is abundantly expressed in the cytoplasm of hESCs and essential for hESC self-renewal. GAS5 depletion in hESCs significantly impaired their pluripotency and self-renewal ability, whereas GAS5 overexpression in hESCs accelerated the cell cycle, enhanced their colony formation ability and increased pluripotency marker expression. By RNA sequencing and bioinformatics analysis, we determined that GAS5 activates NODAL-SMAD2/3 signaling by sustaining the expression of NODAL, which plays a key role in hESC self-renewal but not in somatic cell growth. Further studies indicated that GAS5 functions as a competing endogenous RNA (ceRNA) to protect NODAL mRNA against degradation and that GAS5 transcription is directly controlled by the core pluripotency transcriptional factors (TFs). Taken together, we suggest that the core TFs, GAS5 and NODAL-SMAD2/3 form a feed-forward loop to maintain the hESC self-renewal process. These findings are specific to ESCs and did not occur in the somatic cell lines we tested; therefore, our findings also provide evidence that the functions of lncRNAs vary in different biological contexts. We analyzed long non-coding RNAs in two hESC cell lines (X-01 and H1), and found GAS5 is highly expressed and functional in maintaining hESC self-renewal. We generate stable overexpressed or knockdown hESC cell lines using lentiviral approach. We transfected cells initialy after passage, and lentiviruses are added with daily medium change for three days (at a final concentration of 10^5 IU/ml). Puromycin is added for selection and supplied with daily medium change. Stable cell lines are established after two passages and verified under fluorescence scope. Total RNAs and miRNAs are extracted separately of all three cell lines (LV-NC, LV-GAS5 and LV-shGAS5) and put to sequencing.
2016-03-17 | E-GEOD-66993 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) are recently characterized players that are involved in the regulatory circuitry of self-renewal in human embryonic stem cells (hESCs). However, the specific roles of lncRNAs in this circuitry are poorly understood. Here, we determined that growth-arrest-specific transcript 5 (GAS5), which is a known tumor suppressor and growth arrest gene, is abundantly expressed in the cytoplasm of hESCs and essential for hESC self-renewal. GAS5 depletion in hESCs significantly impaired their pluripotency and self-renewal ability, whereas GAS5 overexpression in hESCs accelerated the cell cycle, enhanced their colony formation ability and increased pluripotency marker expression. By RNA sequencing and bioinformatics analysis, we determined that GAS5 activates NODAL-SMAD2/3 signaling by sustaining the expression of NODAL, which plays a key role in hESC self-renewal but not in somatic cell growth. Further studies indicated that GAS5 functions as a competing endogenous RNA (ceRNA) to protect NODAL mRNA against degradation and that GAS5 transcription is directly controlled by the core pluripotency transcriptional factors (TFs). Taken together, we suggest that the core TFs, GAS5 and NODAL-SMAD2/3 form a feed-forward loop to maintain the hESC self-renewal process. These findings are specific to ESCs and did not occur in the somatic cell lines we tested; therefore, our findings also provide evidence that the functions of lncRNAs vary in different biological contexts.
2016-03-17 | GSE66993 | GEO
Project description:Increasing studies show that long non-coding RNAs (lncRNAs) play essential roles in various fundamental processes. Long non-coding RNA growth arrest-specific transcript 5 (GAS5) showed differential expressions between young and old mouse brains in our previous RNA-Seq data, suggesting its potential role in senescence and brain aging. Examination using RT-qPCR revealed that GAS5 had a significantly higher expression level in old mouse brain hippocampus region than the young one. Cellular fractionation using hippocampus-derived HT22 cell line confirmed its nucleoplasm and cytoplasm subcellular localization. We then performed overexpression (OE) or knockdown (KD) of GAS5 in HT22 cell line and found that GAS5 inhibits cell cycle progression and promotes cell apoptosis. RNA-Seq analysis of GAS5-knockdown HT22 cell identified differential expressed genes related to cell proliferation (e.g., DNA replication and nucleosome assembly biological processes). RNA pull-down assay using mouse brain hippocampus tissues revealed that potential GAS5 interacting proteins can be enriched into several KEGG pathways and some of them are involved in senescence associated diseases such as Parkinson and Alzheimer's Disease. These results contribute to better understand the underlying functional network of GAS5 and its interacting proteins in senescence at brain tissue and brain-derived cell line levels. Our study may also provide reference for developing diagnostic and clinic biomarkers of GAS5 in senescence and brain aging.
2020-12-16 | GSE163237 | GEO
Project description:YAP is an oncogene and an inducer of Epithelial-to-Mesenchymal Transition (EMT). We used microarrays to detail the global program of gene expression to identify YAP target genes. PUBLICATION ABSTRACT: The Hippo pathway defines a novel signaling cascade regulating cell proliferation and survival in Drosophila, which involves the negative regulation of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal amplification locus in mouse and human cancers, and that it mediates dramatic transforming activity in MCF10A primary mammary epithelial cells. Here we show that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 phenocopies YAP overexpression. Since this effect can be suppressed by simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 in mammalian cells. Expression profiling of genes induced by ectopic expression of YAP or by knockdown of LATS1 reveals a subset of potential Hippo pathway targets implicated in epithelial-to-mesenchymal transition (EMT), suggesting that this is a key feature of YAP signaling in mammalian cells. Keywords: vector vs. YAP comparison
2008-01-31 | GSE10196 | GEO
Project description:Microarray analyses with cells/tissues overexpressing YAP have revealed many transcription targets of YAP (Dong et al, 2007; Zhao et al, 2008). However, as YAP induces transformation of non-cancerous cells, we thought many of known targets of YAP may be indirect consequence of transforming property of YAP. To identify the immediate transcription targets for YAP, we utilized immortalized mammary epithelial MCF-10A cells expressing a tamoxifen inducible, hyperactive (S127/381A) YAP mutant (MCF-10A ERT2-YAP 2SA).
2015-11-23 | GSE60579 | GEO