Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al.
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ABSTRACT:
SUBMITTER: He C
PROVIDER: S-EPMC8636738 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Studies have shown that aluminum (Al) is the most abundant neurotoxic element on Earth, and is implicated in the pathogenesis of Alzheimer's disease (AD). However, the mechanisms underlying Al-induced neurotoxicity are still largely elusive. Based on affinity analyses with Al and LC-LTQ-MS, we have found that serum albumin, brain CK-B and 14-3-3ζ protein have a high affinity for Al3+, and albumin has a much stronger affinity for Al than transferrin. The normal activity of CK-B, and physiological combination of 14-3-3ζ with tau can be severely perturbed by Al. We anticipate that our assay will provide a new focus concerning the mechanism underlying Al-induced neurotoxicity, and aid the design of strategies to prevent AD and other human diseases related to Al overload.
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Project description:Gene expression profiling in soybean under aluminum stress: genes differentially expressed between Al-tolerant and Al-sensitive genotypes. Aluminum toxicity is the most important constraint of crop production on acid soils. Understanding the molecular and genetic mechanisms of tolerance is crucial for developing efficient breeding programs to improve Al tolerance. This research was undertaken to identify candidate Al-tolerance genes in soybean. Two soybean genotypes PI 416937 (Al-tolerant) and Young (Al-sensitive) seedlings were exposed to zero or 10 µM Al in a growth chamber under hydroponic conditions for four time spans of 2, 12, 48 or 72 hrs. Microarray analysis was made on mRNA isolated from 1 cm long tap root tips using an Affymetrix soybean genome array. Both novel and previously reported aluminum-responsive genes were identified. The differentially expressed genes were enriched for metabolism, stress response and transporters. Multiple putative Al-tolerance genes uniquely induced in the tolerant genotype includes the up-regulation of previously identified transcription factors auxin down regulated-like protein (ADR6-like) and basic leucine zipper (bZIP 94), sulfur transmembrane transport protein and lipid transfer protein (Sec 14 ) and novel genes that include rare cold inducible protein (RCI2B ), GPI-transamidase, malonyl-COA: Isoflavone 7-O-glucoside-6˝-O-malontransferase, a cell proliferation protein (WPP2), Oleosin protein, pectinestrease inhibitor, and impaired sucrose induction1. The genes identified in this study will be utilized as important genetic resources for future improvement of Al tolerance in soybean. Key words: Soybean, Al tolerance, gene expression, microarray
2011-10-07 | GSE18517 | GEO
Project description:In the search for sustainable energy storage systems, aluminum dual-ion batteries have recently attracted considerable attention due to their low cost, safety, high energy density (up to 70 kWh kg-1), energy efficiency (80-90%) and long cycling life (thousands of cycles and potentially more), which are needed attributes for grid-level stationary energy storage. Overall, such batteries are composed of aluminum foil as the anode and various types of carbonaceous and organic substances as the cathode, which are immersed in an aluminum electrolyte that supports efficient and dendrite-free aluminum electroplating/stripping upon cycling. Here, we review current research pursuits and present the limitations of aluminum electrolytes for aluminum dual-ion batteries. Particular emphasis is given to the aluminum plating/stripping mechanism in aluminum electrolytes, and its contribution to the total charge storage electrolyte capacity. To this end, we survey the prospects of these stationary storage systems, emphasizing the practical hurdles of aluminum electrolytes that remain to be addressed.
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Project description:MicroRNAs (miRNAs) play multiple roles in tumor biology. Interestingly, reports from multiple groups suggest that miRNA targets may be coupled through competitive stoichiometric sequestration. Specifically, computational models predicted and experimental assays confirmed that miRNA activity is dependent on miRNA target abundance, and consequently, changes in the abundance of some miRNA targets lead to changes to the regulation and abundance of their other targets. The resulting indirect regulatory influence between miRNA targets resembles competition and has been dubbed competitive endogenous RNA (ceRNA). Recent studies have questioned the physiological relevance of ceRNA interactions, our ability to accurately predict these interactions, and the number of genes that are impacted by ceRNA interactions in specific cellular contexts.To address these concerns, we reverse engineered ceRNA networks (ceRNETs) in breast and prostate adenocarcinomas using context-specific TCGA profiles, and tested whether ceRNA interactions can predict the effects of RNAi-mediated gene silencing perturbations in PC3 and MCF7 cells._ENREF_22 Our results, based on tests of thousands of inferred ceRNA interactions that are predicted to alter hundreds of cancer genes in each of the two tumor contexts, confirmed statistically significant effects for half of the predicted targets.Our results suggest that the expression of a significant fraction of cancer genes may be regulated by ceRNA interactions in each of the two tumor contexts.
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Project description:Circular RNAs (circRNAs) are a new class of covalently closed circular RNA molecules that are involved in many biological processes. However, information about circRNAs in the pineal gland, particularly that of rats, is limited. To establish resources for the study of the rat pineal gland, we performed transcriptome analysis of the pineal glands during the day and night. In this study, 1413 circRNAs and 1989 miRNAs were identified in the pineal gland of rats during the night and day using the Illumina platform. Forty differentially expressed circRNAs and 93 differentially expressed miRNAs were obtained, among which 20 circRNAs and 37 miRNAs were significantly upregulated during the day and 20 circRNAs and 56 miRNAs were significantly upregulated during the night. As circRNAs have been reported to work as miRNA sponges, we predicted 15940 interactions among 40 circRNAs, 93 miRNAs and 400 mRNAs with differential diurnal expression using miRanda and TargetScan to build a ceRNA regulatory network in the rat pineal gland. The diurnal expression profile of circRNAs in the rat pineal gland may provide additional information about the role of circRNAs in regulating changes in melatonin circadian rhythms. The analyzed data reported in this study will be an important resource for future studies to elucidate the altered physiology of circRNAs in diurnal rhythms.
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Project description:Gene expression profiling in soybean under aluminum stress: genes differentially expressed between Al-tolerant and Al-sensitive genotypes. Aluminum toxicity is the most important constraint of crop production on acid soils. Understanding the molecular and genetic mechanisms of tolerance is crucial for developing efficient breeding programs to improve Al tolerance. This research was undertaken to identify candidate Al-tolerance genes in soybean. Two soybean genotypes PI 416937 (Al-tolerant) and Young (Al-sensitive) seedlings were exposed to zero or 10 µM Al in a growth chamber under hydroponic conditions for four time spans of 2, 12, 48 or 72 hrs. Microarray analysis was made on mRNA isolated from 1 cm long tap root tips using an Affymetrix soybean genome array. Both novel and previously reported aluminum-responsive genes were identified. The differentially expressed genes were enriched for metabolism, stress response and transporters. Multiple putative Al-tolerance genes uniquely induced in the tolerant genotype includes the up-regulation of previously identified transcription factors auxin down regulated-like protein (ADR6-like) and basic leucine zipper (bZIP 94), sulfur transmembrane transport protein and lipid transfer protein (Sec 14 ) and novel genes that include rare cold inducible protein (RCI2B ), GPI-transamidase, malonyl-COA: Isoflavone 7-O-glucoside-6˝-O-malontransferase, a cell proliferation protein (WPP2), Oleosin protein, pectinestrease inhibitor, and impaired sucrose induction1. The genes identified in this study will be utilized as important genetic resources for future improvement of Al tolerance in soybean. Key words: Soybean, Al tolerance, gene expression, microarray Two genotypes: PI 416937 (p) and Young (y); two treatments: aluminum or untreated; four time points: 2, 12, 48, and 72 hrs; 2 or 3 replicates.
2011-10-06 | E-GEOD-18517 | biostudies-arrayexpress
Project description:Alzheimer's disease (AD) is the most common form of dementia worldwide. Accumulating evidence indicates that non-coding RNAs are strongly implicated in AD-associated pathophysiology. However, the role of these ncRNAs remains largely unknown. In the present study, we used microarray analysis technology to characterize the expression patterns of circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs in hippocampal tissue from Aβ1-42-induced AD model rats, to integrate interaction data and thus provide novel insights into the mechanisms underlying AD. A total of 555 circRNAs, 183 miRNAs and 319 mRNAs were identified to be significantly dysregulated (fold-change ≥ 2.0 and p-value < 0.05) in the hippocampus of AD rats. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of randomly-selected circRNAs, miRNAs and mRNAs. Next, GO and KEGG pathway analyses were performed to further investigate ncRNAs biological functions and potential mechanisms. In addition, we constructed circRNA-miRNA and competitive endogenous RNA (ceRNA) regulatory networks to determine functional interactions between ncRNAs and mRNAs. Our results suggest the involvement of different ncRNA expression patterns in the pathogenesis of AD. Our findings provide a novel perspective for further research into AD pathogenesis and might facilitate the development of novel therapeutics targeting ncRNAs.
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Project description:Contrast-induced acute kidney injury (CI-AKI) is a severe complication of intravascular applied radial contrast media, and recent progress in interventional therapy and angiography has revived interest in explaining detailed mechanisms and developing effective treatment. Recent studies have indicated a potential link between CI-AKI and microRNA (miRNA). However, the potential non-coding RNA-associated-competing endogenous RNA (ceRNA) pairs involved in CI-AKI still remain unclear. In this study, we systematically explored the circRNA or lncRNA-associated-ceRNA mechanism in a new rat model of CI-AKI through deep RNA sequencing. The results revealed that the expression of 38 circRNAs, 12 lncRNAs, 13 miRNAs and 127 mRNAs were significantly dysregulated. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses for mRNAs with significantly different expression and then constructed comprehensive circRNA or lncRNA-associated ceRNA networks in kidney of CI-AKI rats. Thereafter, two constructed ceRNA regulatory pathways in this CI-AKI rat model-novel_circ_0004153/rno-miR-144-3p/Gpnmb or Naglu and LNC_000343/rno-miR-1956-5p/KCP-were validated by real-time qPCR. This study is the first one to provide a systematic dissection of non-coding RNA-associated ceRNA profiling in kidney of CI-AKI rats. The selected non-coding RNA-associated ceRNA networks provide new insight for the underlying mechanism and may profoundly affect the diagnosis and therapy of CI-AKI.
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Project description:Osteoporosis increases the risk of fracture. Improving the diagnosis and treatment of osteoporosis has clinical applications. The differentially expressed genes (DEcircRs, DEmRs, DEmiRs) of osteoporotic patients and controls were analyzed using the GEO database, and enrichment analysis of DEmRs was performed. circRNAs and mRNAs, which were predicted to have a target relationship with DEmRs, were obtained to compare competing endogenous RNA (ceRNA) regulatory networks by comparison with differentially expressed genes. Molecular experiments were utilized to validate the expression of genes within the network. The interactions between genes within the ceRNA network were validated by luciferase reporter assays. Following overexpression of circ_0070304 in bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of the cells was assessed by Alizarin Red staining. A total of 110 intersectional DEmRs between patients with osteoporosis and controls from GSE35958 and GSE56815, which were mainly enriched in estrogen, the thyroid hormone signaling pathway, and adherens junctions were identified. A ceRNA network [circ_0070304/miR‑183‑5p/ring finger and CCCH‑type domains 2 (RC3H2)] was then constructed. Circ_0070304 acted as a sponge for miR‑183‑5p and regulated RC3H2 expression. Overexpression of circ_0070304 upregulated ROCK1 and induced osteogenic differentiation. The ceRNA regulatory network that was obtained is expected to be a new target for osteoporosis treatment and to provide new insights into the diagnosis and treatment of osteoporosis in greater depth.
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Project description:BackgroundAdult degenerative scoliosis (ADS) is forecast to be a prevalent disabling condition in an aging society. Universally, its pathogenesis is perceived as intervertebral disc degeneration (IDD), however, a thought-provoking issue is why precisely a subset of patients with disc degeneration develop ADS. Exploring the diversities between common IDD and ADS would contribute to unraveling the etiological mechanisms of ADS. Therefore, we aimed to integrate the circRNA, lncRNA, miRNA, and mRNA expression profiles from normal adults (Normal), patients with lumbar disc herniation (LDH), and ADS by whole transcriptome sequencing, which identifies critical functional ncRNA and ceRNA networks and crosstalk between the various transcripts.MethodsThe fresh whole blood samples (n = 3/group) were collected from ADS patients, LDH patients, and healthy volunteers (Normal group), which were examined for mRNA, miRNA, lncRNA, and circRNA expression and screened for differentially expressed (DE) ncRNAs. Then, Gene Ontology (GO) and KEGG analyses were performed for gene annotation and enrichment pathways on the DE RNAs, which were constructed as a lncRNA-miRNA-mRNA network. Eventually, DE RNAs were validated by qRT-PCR targeting disc nucleus pulposus (NP) tissue in ADS and LDH group (n = 10/group).ResultsCompared to the LDH group, we identified 3322 DE mRNAs, 221 DE lncRNAs, 20 DE miRNAs, and 15 DE circRNAs in the ADS. In contrast to Normal, 21 miRNAs and 19 circRNAs were differentially expressed in the ADS. The expression of multiple differentially expressed ncRNAs was confirmed by qRT-PCR analysis to be consistent with the sequencing results. In addition, GO, and KEGG analysis demonstrated that most DE mRNAs and ncRNAs target genes are involved in various biological processes, including Endocytosis, Apoptosis, Rap1 signaling pathway, Notch signaling pathway, and others. The constructed lncRNA-miRNA-mRNA co-expression network was primarily related to angiogenesis and regulation.ConclusionBy focusing on comparing asymmetric and symmetric disc degeneration, whole-transcriptome sequencing and bioinformatics analysis systematically screened for key ncRNAs in the development of ADS, which provided an abundance of valuable candidates for the elucidation of regulatory mechanisms. The DE ncRNAs and the lncRNA-miRNA-mRNA network are intrinsically involved in the regulation of mediator and angiogenesis, which may contribute to the insight into the pathogenesis of ADS.
| S-EPMC10098162 | biostudies-literature