The long non-coding RNA GAS5 differentially regulates cell cycle arrest and apoptosis in human neuroblastoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE90523 | GEO | 2016/11/26
SECONDARY ACCESSION(S): PRJNA354960
REPOSITORIES: GEO
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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: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:The long non-coding RNA GAS5 has been shown to modulate cancer proliferation in numerous human cancer systems and has been correlated with successful patient outcome. Our examination of GAS5 in neuroblastoma has revealed robust expression in both MYCN-amplified and non-amplified cell lines. Knockdown of GAS5 In vitro resulted in defects in cell proliferation, apoptosis, and induced cell cycle arrest. Further analysis of GAS5 clones revealed multiple novel splice variants, two of which inversely modulated with MYCN status. Complementation studies of the variants post-knockdown of GAS5 indicated alternate phenotypes, with one variant (FL) considerably enhancing cell proliferation by rescuing cell cycle arrest and the other (C2) driving apoptosis, suggesting a unique role for each in neuroblastoma cancer physiology. Global sequencing and ELISA arrays revealed that the loss of GAS5 induced p53, BRCA1, and GADD45A, which appeared to modulate cell cycle arrest in concert. Complementation with only the FL GAS5 clone could rescue cell cycle arrest, stabilizing HDM2, and leading to the loss of p53. Together, these data offer novel therapeutic targets in the form of lncRNA splice variants for separate challenges against cancer growth and cell death.
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Project description:Single-color gene expression profiles from 2 neuroblastoma cell lines were generated using 44K oligonucleotide microarrays. To gain insights into the molecular processes occurring upon HOXC9 re-expression, we analyzed gene expression profiles of IMR-32 and SK-N-AS cells after Hox-C9 induction using microarrays. We used gene ontology (GO) annotations to find classes of genes that are significantly over-represented in gene sets that were either up- or downregulated after HOXC9 re-expression. One-color gene expression analysis Single-color gene expression profiles from 2 neuroblastoma cell lines were generated using 44K oligonucleotide microarrays. Total RNA of HOXC9- and GFP-expressing SK-N-AS and IMR-32 cells was isolated at 0, 6, 12, 24, 48 and 96 h using Trizol. To determine global differences in the expression profiles of HOXC9- and GFP-induced SK-N-AS and IMR-32 cells, mean expression levels of each gene between HOXC9-induced and control (GFP) cells were compared. Gene Ontology Tree Machine (GOTM) was used to identify functional categories associated with the condition of the respective cell line.
2013-03-28 | E-GEOD-45545 | biostudies-arrayexpress
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:IMR-32 cells were subjected to lentiviral YRNA infection or nELAVL RNAi and/or UV stress followed by RNAseq analysis to monitor RNA level changes RNA from IMR-32 cells was Trizol extracted, Ribominus selected and submitted for high-throughput sequencing.
2016-02-17 | E-GEOD-53698 | biostudies-arrayexpress
Project description:Vascular remodeling is a pathological process following cardiovascular intervention. Vascular smooth muscle cells (VSMC) play a critical role in the vascular remodeling. Long noncoding RNAs (lncRNA) are a class of gene regulators functioning through various mechanisms in physiological and pathological conditions. By using cultured VSMC and rat carotid artery balloon injury model, we found that lncRNA growth arrest specific 5 (GAS5) serves as a negative regulator for VSMC survival in vascular remodeling. By manipulating GAS5 expression via adenoviral overexpression or short hairpin RNA knockdown, we found that GAS5 suppresses VSMC proliferation while promoting cell cycle arrest and inducing cell apoptosis. Mechanistically, GAS5 directly binds to p53 and p300, stabilizes p53-p300 interaction, and thus regulates VSMC cell survival via induction of p53-downstream target genes. Importantly, local delivery of GAS5 via adenoviral vector suppresses balloon injury-induced neointima formation along with an increased expression of p53 and apoptosis in neointimal SMCs. Our study demonstrated for the first time that GAS5 negatively impacts VSMC survival via activation the p53 pathway during vascular remodeling.
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Project description:The human neuroblastoma cell lines SH-SY5Y and IMR-32 can be differentiated into neuron-like phenotypes through treatment with all-trans retinoic acid (ATRA). After differentiation, these cell lines are extensively utilized as in vitro models to study various aspects of neuronal cell biology. However, temporal and quantitative profiling of the proteome and phosphoproteome of SH-SY5Y and IMR-32 cells throughout ATRA-induced differentiation has been limited. Here, we performed relative quantification of the proteomes of SH-SY5Y and IMR-32 cells at multiple time points during ATRA-induced differentiation. The data presented serve as a valuable resource for investigating temporal protein and phosphoprotein abundance changes in SH-SY5Y and IMR-32 cells during ATRA-induced differentiation.
2024-01-24 | PXD046900 | Pride
Project description:The human neuroblastoma cell lines SH-SY5Y and IMR-32 can be differentiated into neuron-like phenotypes through treatment with all-trans retinoic acid (ATRA). After differentiation, these cell lines are extensively utilized as in vitro models to study various aspects of neuronal cell biology. However, temporal and quantitative profiling of the proteome and phosphoproteome of SH-SY5Y and IMR-32 cells throughout ATRA-induced differentiation has been limited. Here, we performed relative quantification of the phosphoproteomes of SH-SY5Y and IMR-32 cells at multiple time points during ATRA-induced differentiation. The data presented serve as a valuable resource for investigating temporal protein and phosphoprotein abundance changes in SH-SY5Y and IMR-32 cells during ATRA-induced differentiation.
2024-01-24 | PXD046871 | Pride
Project description:Single-color gene expression profiles from IMR-32 neuroblastoma cell lines were generated using 44K oligonucleotide microarrays. To gain insights into the molecular processes occurring upon TFAP2B re-expression, we performed gene expression measurements in TFAP2B and GFP expressing transgenic IMR-32 neuroblastoma cell lines at d2 and d7 of transgene induction.
2015-10-27 | GSE74350 | GEO