Dataset Information

Whole-Transcriptome Analysis of APP/PS1 Mouse Brain and Identification of circRNA-miRNA-mRNA Networks to Investigate AD Pathogenesis.

ABSTRACT: Alzheimer's disease (AD) is one of the most common forms of dementia and is characterized by a progressive loss of cognition. A hallmark of AD is known to be the extensive distribution of neuronal tangles and amyloid plaques in the brain, but the molecular and cellular complexity of AD remains poorly elucidated, which limits the development of effective clinical treatments for AD. Accumulating evidence indicates that noncoding RNAs participate in AD-associated pathophysiology, but the details are largely unknown. Moreover, although recent studies have revealed a potential link between AD and circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) networks, few genome-wide studies have identified putative circRNA-associated ceRNA pairs involved in AD. Here, we used deep RNA sequencing to systematically investigate circRNA-associated ceRNA mechanisms in the brain of AD model mice (APP/PS1). Our results identified 235, 30, and 1,202 significantly dysregulated circRNAs, microRNAs (miRNAs), and mRNAs, respectively, and we used the sequencing data to construct the most comprehensive circRNA-associated ceRNA networks to date in the APP/PS1 brain. Gene Ontology (GO) analysis revealed that the identified networks are involved in regulating AD development from distinct origins, such as from the dendrite (GO: 0030425) and the synapse (GO: 0045202). Following rigorous selection, the circRNA-associated ceRNA networks in this AD mouse model were discovered to be mainly involved in dendritic development and memory (Sorbs2) and mouse neural development (ALS2). This study presents the first systematic dissection of circRNA-associated ceRNA profiles in the APP/PS1 mouse brain, and the identified circRNA-associated ceRNA networks could provide insights that facilitate AD diagnosis and therapy in the future.

SUBMITTER: Ma N

PROVIDER: S-EPMC6906698 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Whole-Transcriptome Analysis of APP/PS1 Mouse Brain and Identification of circRNA-miRNA-mRNA Networks to Investigate AD Pathogenesis.

Ma Nana N Pan Jie J Ye Xiaoyang X Yu Bo B Zhang Wei W Wan Jun J

Molecular therapy. Nucleic acids 20191106

Alzheimer's disease (AD) is one of the most common forms of dementia and is characterized by a progressive loss of cognition. A hallmark of AD is known to be the extensive distribution of neuronal tangles and amyloid plaques in the brain, but the molecular and cellular complexity of AD remains poorly elucidated, which limits the development of effective clinical treatments for AD. Accumulating evidence indicates that noncoding RNAs participate in AD-associated pathophysiology, but the details ar ...[more]

PMID: 31786335

Similar Datasets

Project description:BackgroundCircular RNAs (circRNAs) are a new class of noncoding RNAs that have gained increased attention in human tumor research. However, the identification and function of circRNAs are largely unknown in the context of gastric cancer (GC). This study aims to identify novel circRNAs and determine their action networks in GC.MethodsA comprehensive strategy of data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology were conducted to discover novel circRNAs and to explore their potential mechanisms in GC. Promising therapeutic drugs for GC were determined by connectivity map (CMap) analysis.ResultsSix overlapped differentially expressed circRNAs (DECs) were screened from selected microarray and RNA-Seq datasets of GC, and the six DECs were then validated by sanger sequencing and RNase R treatment. Subsequent RT-qPCR analysis of GC samples confirmed decreased expressions of the six DECs (hsa_circ_0000390, hsa_circ_0000615, hsa_circ_0001438, hsa_circ_0002190, hsa_circ_0002449 and hsa_circ_0003120), all of which accumulated preferentially in the cytoplasm. MiRNA binding sites and AGO2 occupation of the six circRNAs were predicted using online databases, and circRNA-miRNA interactions including the six circRNAs and 33 miRNAs were determined. Then, 5320 target genes of the above 33 miRNAs and 1492 differently expressed genes (DEGs) from The Cancer Genome Atlas (TCGA) database were identified. After intersecting the miRNA target genes and the 889 downregulated DEGs, 320 overlapped target genes were acquired. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these target genes were related to two critical tumor-associated signaling pathways. A protein-protein interaction network with the 320 target genes was constructed using STRING, and fifteen hubgenes (ATF3, BTG2, DUSP1, EGR1, FGF2, FOSB, GNAO1, GNAI1, GNAZ, GNG7, ITPR1, ITPKB, JUND, NR4A3, PRKCB) in the network were identified. Finally, bioactive chemicals (including vorinostat, trichostatin A and astemizole) based on the fifteen hubgenes were identifed as therapeutic agents for GC through the CMap analysis.ConclusionsThis study provides a novel insight for further exploration of the pathogenesis and therapy of GC from the circRNA-miRNA-mRNA network perspective.

Project description:Coxsackievirus A16 (CV-A16) has caused worldwide epidemics of hand, foot, and mouth disease (HFMD) in infants and preschool children. Circular RNAs (circRNAs), a class of noncoding RNA molecules, participate in the progression of viral infectious diseases. Although the function of circRNAs has been a heavily researched topic, their role in CV-A16 infection is still unclear. In this study, the viral effects of CV-A16 on the cellular circRNA transcriptome were investigated using next-generation sequencing technology. The results showed that a total of 8726, 8611, and 6826 circRNAs were identified at 0, 12, and 24 h postinfection, respectively. Moreover, it was found that 1769 and 1192 circRNAs were differentially expressed in at 12 and 24 h postinfection, respectively. The common differentially expressed circRNAs were used for functional annotation analysis, and it was found that the parent genes of differentially expressed circRNAs might be associated with the viral infection process, especially the "Immune system process" in GO analysis and the "Inflammation mediated by chemokine and cytokine signaling pathway" in KEGG analysis. Subsequently, circRNA-miRNA-mRNA regulatory networks were constructed, and the hsa_circ_0004447/hsa-miR-942-5p/MMP2, hsa_circ_0078617/hsa-miR-6780b-5p/MMP2 and hsa_circ_0078617/hsa-miR-5196-5p/MMP2 regulatory axes were identified by enrichment analysis as important networks during the progression of CV-A16 infection. Finally, six dysregulated circRNAs were selected for validation and were verified to be consistent with the sequencing results. Considering all of these results, to the best of our knowledge, this study is the first to present a comprehensive overview of circRNAs induced by CV-A16 infection, and this research demonstrated that a network of enriched circRNAs and circRNA-associated competitive endogenous RNAs (ceRNAs) is involved in the regulation of CV-A16 infection, thereby helping to elucidate the mechanisms underlying CV-A16-host interactions.

Dataset Information

Whole-Transcriptome Analysis of APP/PS1 Mouse Brain and Identification of circRNA-miRNA-mRNA Networks to Investigate AD Pathogenesis.

Publications

Whole-Transcriptome Analysis of APP/PS1 Mouse Brain and Identification of circRNA-miRNA-mRNA Networks to Investigate AD Pathogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets