Dataset Information

Characterization of circRNA-Associated-ceRNA Networks in a Senescence-Accelerated Mouse Prone 8 Brain.

ABSTRACT: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Although many researchers have attempted to explain the origins of AD, developing an effective strategy in AD clinical therapy is difficult. Recent studies have revealed a potential link between AD and circRNA-associated-ceRNA networks. However, few genome-wide studies have identified the potential circRNA-associated-ceRNA pairs involved in AD. In this study, we systematically explored the circRNA-associated-ceRNA mechanism in a 7-month-old senescence-accelerated mouse prone 8 (SAMP8) model brain through deep RNA sequencing. We obtained 235 significantly dysregulated circRNA transcripts, 30 significantly dysregulated miRNAs, and 1,202 significantly dysregulated mRNAs. We then constructed the most comprehensive circRNA-associated-ceRNA networks in SAMP8 brain. GO analysis revealed that these networks were involved in regulating the development of AD from various angles, for instance, axon terminus (GO: 0043679) and synapse (GO: 0045202). Following rigorous selection, we discovered that the circRNA-associated-ceRNA networks in this AD mouse model were mainly involved in the regulation of A? clearance (Hmgb2) and myelin function (Dio2). This research is the first to provide a systematic dissection of circRNA-associated-ceRNA profiling in SAMP8 mouse brain. The selected circRNA-associated-ceRNA networks can profoundly affect the diagnosis and therapy of AD in the future.

SUBMITTER: Zhang S

PROVIDER: S-EPMC5589091 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Characterization of circRNA-Associated-ceRNA Networks in a Senescence-Accelerated Mouse Prone 8 Brain.

Zhang Shuai S Zhu Dina D Li Hong H Li Hejian H Feng Chengqiang C Zhang Wensheng W

Molecular therapy : the journal of the American Society of Gene Therapy 20170629 9

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Although many researchers have attempted to explain the origins of AD, developing an effective strategy in AD clinical therapy is difficult. Recent studies have revealed a potential link between AD and circRNA-associated-ceRNA networks. However, few genome-wide studies have identified the potential circRNA-associated-ceRNA pairs involved in AD. In this study, we systematically explored the circRNA-associated-ceRNA mec ...[more]

PMID: 28669840

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Project description:BackgroundJuvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16. The study aimed to identify key genes and pathways that are influenced by circRNAs and to screen potential therapeutic agents for JSpA. The study involved the analysis of circRNA expression profiles, identification of circRNA-miRNA-mRNA regulatory networks, and functional annotation of differentially expressed genes. The results of the study may have provided insights into the molecular mechanisms underlying JSpA and potential therapeutic targets for this disease.MethodsIn this study, sequencing data of circRNA, miRNA, and mRNA were obtained from the GEO datasets. The data were then analyzed to identify candidates for constructing a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Functional enrichments of genes were performed using the DAVID database. A PPI network was constructed using the STRING database and visualized using Cytoscape software. The MCODE plugin app was used to explore hub genes in the PPI network. The expression changes in immune cells were assessed using the online CIBERSORT algorithm to obtain the proportion of various types of immune cells. Finally, the Connectivity Map L1000 platform was used to identify potential agents for JSpA treatment. Overall, this study aimed to provide a comprehensive understanding of the molecular mechanisms underlying JSpA and to identify potential therapeutic agents for this disease.ResultsA total of 225 differentially expressed circRNAs (DEcircRNAs), 23 differentially expressed miRNAs (DEmiRNAs) and 1324 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 5 overlapped circRNAs, 7 miRNAs and 299 target mRNAs into a circRNA-miRNA-mRNA network. We next identified 10 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with JAK-STAT signal pathway. We found that neutrophils accounted for the majority of all enriched cells. In addition, we discovered several chemicals as potential treatment options for JSpA.ConclusionsThrough this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of JSpA from the view of a competitive endogenous RNA (ceRNA) network.

Project description:Postoperative cognitive dysfunction (POCD) is a clinical entity associated with declined cognitive function following surgery. It occurs more frequently in elderly patients. Recent studies have shown that circRNA-associated-ceRNA networks, constructed based on interactions between circRNA-miRNA and miRNA-mRNA, provide key insight into the molecular mechanisms underlying the pathogenesis of several neurological diseases. However, the mechanism of POCD remains undetermined. In this study, laparotomies were performed under isoflurane anesthesia on young (2-month-old) and aging (17-month-old) male C57BL/6 mice. The results showed that the aging mice were more likely than the young mice to develop POCD. Subsequently, differentially expressed circRNAs, miRNAs, and mRNAs were characterized by RNA sequencing the hippocampi of young and aging mice under control and surgery conditions. Six circRNAs, 6 miRNAs, and 203 mRNAs were identified to construct the circRNA-associated-ceRNA network for the control condition, while 13 circRNAs, 8 miRNAs, and 189 mRNAs were used for the circRNA-associated-ceRNA network for the surgery condition. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of these two networks revealed that the circRNA-associated-ceRNA networks are involved in POCD pathogenesis though modulating the Wnt and VEGF signaling pathways, as well as neural processes associated with long-term synaptic depression and synaptic transmission. In particular, the mmu-miR-298-5P regulatory pathway identified in this study's mouse model suggests that mm9_circ_009789- and mm9_circ_004229-associated-ceRNA networks as closely related to the occurrence of POCD through regulating PKC signaling pathway, neural cell apoptosis and glycolipid metabolism pathway. These findings provide possible insight into the role of the circRNA-associated-ceRNA networks, helping to unravel the complexity of the molecular pathogenesis of POCD.

Project description:Background: Alzheimer's disease (AD) is a fatal neurodegenerative disease characterized by progressive cognitive decline and memory loss. However, several therapeutic approaches have shown unsatisfactory outcomes in the clinical setting. Thus, developing alternative therapies for the prevention and treatment of AD is critical. Salidroside (SAL) is critical, an herb-derived phenylpropanoid glycoside compound, has been shown to attenuate lipopolysaccharide (LPS)-induced cognitive impairment. However, the mechanism underlying its neuroprotective effects remains unclear. Here, we show that SAL has a therapeutic effect in the senescence-accelerated mouse prone 8 (SAMP8) strain, a reliable and stable mouse model of AD. Methods: SAMP8 mice were treated with SAL, donepezil (DNP) or saline, and cognitive behavioral impairments were assessed using the Morris water maze (MWM), Y maze, and open field test (OFT). Fecal samples were collected and analyzed by 16S rRNA sequencing on an Illumina MiSeq system. Brain samples were analyzed to detect beta-amyloid (A?) 1-42 (A?1-42) deposition by immunohistochemistry (IHC) and western blotting. The activation of microglia and neuroinflammatory cytokines was detected by immunofluorescence (IF), western blotting and qPCR. Serum was analyzed by a Mouse High Sensitivity T Cell Magnetic Bead Panel on a Luminex-MAGPIX multiplex immunoassay system. Results: Our results suggest that SAL effectively alleviated hippocampus-dependent memory impairment in the SAMP8 mice. SAL significantly 1) reduced toxic A?1-42 deposition; 2) reduced microglial activation and attenuated the levels of the proinflammatory factors IL-1?, IL-6, and TNF-? in the brain; 3) improved the gut barrier integrity and modified the gut microbiota (reversed the ratio of Bacteroidetes to Firmicutes and eliminated Clostridiales and Streptococcaceae, which may be associated with cognitive deficits); and 4) decreased the levels of proinflammatory cytokines, particularly IL-1?, IL-6, IL-17A and IL-12, in the peripheral circulation, as determined by a multiplex immunoassay. Conclusion: In summary, SAL reversed AD-related changes in SAMP8 mice, potentially by regulating the microbiota-gut-brain axis and modulating inflammation in both the peripheral circulation and central nervous system. Our results strongly suggest that SAL has a preventive effect on cognition-related changes in SAMP8 mice and highlight its value as a potential agent for drug development.

Dataset Information

Characterization of circRNA-Associated-ceRNA Networks in a Senescence-Accelerated Mouse Prone 8 Brain.

Publications

Characterization of circRNA-Associated-ceRNA Networks in a Senescence-Accelerated Mouse Prone 8 Brain.

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