Dysregulated long noncoding RNAs in the brainstem of DBA/1 mouse SUDEP model
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE160576 | GEO | 2020/11/01
REPOSITORIES: GEO
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Project description:Dysregulated long noncoding RNAs in the brainstem of DBA/1 mouse SUDEP model
| PRJNA673625 | ENA
Project description:Our study reveals that many lncRNAs and mRNAs were differentially expressed between the brainstem of DBA/1 and C57BL/6 mouse
2020-06-23 | GSE152931 | GEO
Project description:BackgroundLong noncoding RNAs (lncRNAs) play an important role in many neurological diseases. This study aimed to investigate differentially expressed lncRNAs and messenger RNAs (mRNAs) in the susceptibility gaining process of primed DBA/1 mice, a sudden unexpected death in epilepsy (SUDEP) model, to illustrate the potential role of lncRNAs in SUDEP.MethodsThe Arraystar mouse lncRNA Microarray V3.0 (Arraystar, Rockville, MD) was applied to identify the aberrantly expressed lncRNAs and mRNAs between primed DBA/1 mice and normal controls. The differences were verified by qRT-PCR. We conducted gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and coexpression analyses to explore the possible function of the dysregulated RNAs.ResultsA total of 502 lncRNAs (126 upregulated and 376 downregulated lncRNAs) and 263 mRNAs (141 upregulated and 122 downregulated mRNAs) were dysregulated with P < 0.05 and a fold change over 1.5, among which Adora3 and Gstt4 were possibly related to SUDEP. GO analysis revealed that chaperone cofactor-dependent protein refolding and misfolded protein binding were among the top ten downregulated terms, which pointed to Hspa1a, Hspa2a and their related lncRNAs. KEGG analysis identified 28 upregulated and 10 downregulated pathways. Coexpression analysis showed fifteen dysregulated long intergenic noncoding RNAs (lincRNAs) and three aberrantly expressed antisense lncRNAs, of which AK012034 and NR_040757 are potentially related to SUDEP by regulating LMNB2 and ITPR1, respectively.ConclusionsLncRNAs and their coexpression mRNAs are dysregulated in the priming process of DBA/1 in the brainstem. Some of these mRNAs and lncRNAs may be related to SUDEP, including Adora3, Lmnb2, Hspa1a, Hspa1b, Itrp1, Gstt4 and their related lncRNAs. Further study on the mechanism of lncRNAs in SUDEP is needed.
| S-EPMC8369804 | biostudies-literature
Project description:Long noncoding RNA and mRNA expression profile in brainstem of DBA/1 and C57BL/6 mouse
| PRJNA641011 | ENA
Project description:Long noncoding RNAs (lncRNAs) are important regulators of cell fate, and their mis-expression has been implicated in many diseases. While distinct polymerases generate messenger vs. noncoding ribosomal or tRNAs3, little is known about distinct mechanisms controlling lncRNA expression. Here we show that transcription of lncRNAs is quantitatively different from that of messenger RNAs (mRNAs)--as revealed by deficiency of Dicer (Dcr), a key ribonuclease that generates microRNAs (miRNAs). Loss of Dcr in mouse embryonic stem cells (mESCs) led surprisingly to decreased level of the majority of lncRNAs. The canonical Dgcr8-Dcr-miRNA pathway is required for robust lncRNA expression, at the level of transcriptional initiation and elongation of lncRNA genes rather than at the level of their stability. cMyc, an oncogenic transcription factor, whose expression is indirectly regulated by Dcr-miRNA in mESCs, is partly responsible for lncRNA transcription. Loss of cMyc led to a more dramatic decrease of lncRNAs than mRNAs, and cMyc overexpression rescues lncRNA expression in Dcr KO cells. A quantitative metric of “mRNA-lncRNA decoupling” revealed that Dcr and cMyc differentially regulate lncRNAs vs. mRNAs in diverse cell types and in vivo, as evidenced by hundreds of microarray experiments. Thus, Dcr and cMyc may allow numerous lncRNAs to be activated or deactivated as a class, implicating lncRNAs to potential regulatory roles in development and disease states where Dcr and cMyc have been associated with. RNA was sequenced from WT and Dcr KO mESCs and the expression of lncRNAs and mRNAs are compared between WT and Dcr KO mESCs.
2014-06-15 | E-GEOD-55338 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) are generally defined as RNA transcripts longer than 200 nucleotides that are not translated into proteins. Recently, many small open reading frames (smORFs) embedded in lncRNA scripts have been verified to be able to encode functional polypeptides (namely lncRNA-SEPs here). Although collaborative analysis by advanced genomics, bioinformatics and proteomics largely drives SEPs discovery, the poor predictability, diminutive size and low abundance still challenge systematic identification of SEPs from different biological samples. Here, we took advantage of the NONCODE database that deposited with the most complete collection and annotation of lncRNA transcripts from different species to build a database that to maximally collect all putative small ORFs from human and mouse lncRNA transcripts. Two effective and complementary polypeptides enrichment strategies (30 kDa MWCO filter and C8 SPE column) were also integrated to further improve the discovery of novel lncRNA-SEPs. These efforts led to the discovery of 362 lncRNA-SEPs from 8 human cell lines and 238 lncRNA-SEPs from 3 mouse cell lines and 8 mouse tissues. 18 out of these lncRNA-SEPs were verified experimentally by multiple technologies including in vitro expression, immunoblotting and parallel reaction monitoring-based mass spectrometry (PRM-MS) in 293T cells. Further bioinformatic analysis reveals that the physical and chemical properties of these novel lncRNA-SEPs, such as amino acid composition and codon usage, are varied from canonical proteins. Intriguingly, nearly 70% of the identified lncRNA-SEPs were found to be initiated with non-AUG start codons. Collectively, the efficient workflows presented in this study enables us identify 600 novel lncRNA-SPEs from multiple cell lines and tissues, which should represent the largest number of MS-detected lncRNA-encoding SEPs ever reported to date. These novel lncRNA-SEPs not only could provide new clues for the annotation of the noncoding elements in the genome, but also could serve as a valuable resource for the functional characterization of individual lncRNA-SEPs.
2023-05-06 | PXD016981 | Pride
Project description:Maintenance of the drug-addicted state involves changes in gene expression in different neuronal cell types and neural circuits. Midbrain dopamine neurons in particular mediate numerous responses to drugs of abuse. Long noncoding RNAs (lncRNAs) regulate CNS gene expression through a variety of mechanisms, but very little is known about their role in drug abuse. The proportion of lncRNAs that are primate-specific provides a strong rationale for their study in human drug abusers. We examined the profile of lncRNA expression in postmortem human midbrain specimens from chronic cocaine abusers and well-matched control subjects (n=11 subject pairs) using a custom lncRNA microarray. Differential expression was validated by quantitative PCR, and cellular localization investigated by in situ hybridization histochemistry.A profile of lncRNAs significantly dysregulated in chronic cocaine abusers was determined. LncRNAs with dopamine cell-specific expression, differential subcellular distribution, covariance with protein-coding genes, and tissue-specific drug-responsiveness were identified. Dysregulation of midbrain lncRNA expression may reflect pathophysiological processes associated with chronic cocaine abuse. LncRNAs may be central mediators of cellular responses to drug abuse. cRNAs were generated from postmortem human midbrain specimens from chronic cocaine abusers and well-matched control subjects and hybridized to a custom Agilent 4 x 44,000-feature high-density oligonucleotide microarray platform using 60-mer probes. Cocaine control pairs were run together in a dye-flip two-color design, meaning each sample was run in quadruplicate, twice with each dye (Alexa-647 and Alexa-555; Invitrogen, Carlsbad, CA). Microarray slides were scanned with the default Agilent protocol and the intensity of fluorescence between dyes was normalized using a Loess correction. There are 7 probes per gene. Data across all cases and quadruplicates were quantile-normalized.
2015-07-04 | E-GEOD-67281 | biostudies-arrayexpress
Project description:Long noncoding RNAs (lncRNAs) are important regulators of cell fate, and their mis-expression has been implicated in many diseases. While distinct polymerases generate messenger vs. noncoding ribosomal or tRNAs3, little is known about distinct mechanisms controlling lncRNA expression. Here we show that transcription of lncRNAs is quantitatively different from that of messenger RNAs (mRNAs)--as revealed by deficiency of Dicer (Dcr), a key ribonuclease that generates microRNAs (miRNAs). Loss of Dcr in mouse embryonic stem cells (mESCs) led surprisingly to decreased level of the majority of lncRNAs. The canonical Dgcr8-Dcr-miRNA pathway is required for robust lncRNA expression, at the level of transcriptional initiation and elongation of lncRNA genes rather than at the level of their stability. cMyc, an oncogenic transcription factor, whose expression is indirectly regulated by Dcr-miRNA in mESCs, is partly responsible for lncRNA transcription. Loss of cMyc led to a more dramatic decrease of lncRNAs than mRNAs, and cMyc overexpression rescues lncRNA expression in Dcr KO cells. A quantitative metric of “mRNA-lncRNA decoupling” revealed that Dcr and cMyc differentially regulate lncRNAs vs. mRNAs in diverse cell types and in vivo, as evidenced by hundreds of microarray experiments. Thus, Dcr and cMyc may allow numerous lncRNAs to be activated or deactivated as a class, implicating lncRNAs to potential regulatory roles in development and disease states where Dcr and cMyc have been associated with.
2014-06-15 | GSE55338 | GEO
Project description:Age-related hearing loss (AHL) is the progressive loss of auditory function with aging. The DBA/2J (DBA) mice have been used as a model of AHL and undergoes progressive, age-related hearing loss by 12 weeks of age. Here we analyzed cochlear gene expression of 7-week-old and 36-week-old DBA mice using microarrays. Auditory brainstem response (ABR) analysis confrimed that severe age-related hearing loss occured in 36-week-old mice, whereas moderate hearing loss occured in 7-week-old mice. Comprehensive gene expression analysis identified genes correlated with AHL and revealeed that 15 mitochondrial process categories, including “mitochondrial electron transport chain”, “oxidative phosphorylation”, “respiratory chain complex I”, “respiratory chain complex IV”, and “respiratory chain complex V”, were statistically associated with AHL-correlated genes in the cochlea of 36-week-old DBA mice, and that 25 genes encoding components of the mitochondrial respiratory chain (respiratory chain complex I, IV, and V) were significantly down-regulated in the cochlea. These observations provide evidence that AHL is associated with down-regulation of genes involved in the mitochondrial respiratory chain in the cochlea of DBA mice, and suggest that mitochondrial respiratory chain dysfunction may be a key feature of AHL in mammalian cochlea. Keywords: Disease state analysis, Time course analysis
2007-10-16 | GSE6045 | GEO
Project description:Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers, and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM. To identify mRNA and lncRNA biomarkers associated with malignant pleural mesothelioma (MPM), we performed gene expression array analysis on 4 MPM cell lines (H28, MM05, MSTO-211H, H226) compared to the immortalised mesothelial line (MeT-5A). All cell lines were profiled in duplicate. Synthesis of the labelled first strand cDNA was conducted using the Superscript Plus Direct cDNA labeling system with starting material of 10ug total RNA. The labeled dNTP mix was added to the reaction to generate labeled second strand cDNA. Following the hydrolysis reaction, single-stranded cDNA was purified using low elution volume spin cartridges included in the purification module. Samples were labelled using Alexa Fluor 555 dyes. Samples were then hybridised to NCode Long Noncoding RNA Microarrays. Slides were scanned using an Agilent Scanner. Genes differentially expressed between Met-5A and the MPM cell lines were identified on the basis of P-value and fold change.
2013-08-22 | E-GEOD-48174 | biostudies-arrayexpress