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Differential expression and functional analysis of circular RNA in Alzheimer’s disease

ABSTRACT: This study investigated the pathogenesis of Alzheimer’s disease by analyzing the differential expression of circular RNAs (circRNAs), and their interactions with microRNAs (miRNAs). A circRNA microarray was used to screen expressed circRNAs in peripheral blood leukocytes from three patients with AD and four healthy control participants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to annotate the functions of the circRNAs. Changes in expression of six circRNAs [0045808/0070162/0001929/0092270/0092222/0092223]) was confirmed by RT-qPCR, of which three (hsa_circ_[0045808/0070162/0092270]) were further verified by RT-qPCR using a large sample of 23 patients with AD and 25 healthy controls. A circRNA-miRNA-mRNA interaction network, constructed using TargetScan, miRanda, and Cytoscape, revealed upregulated (n=311) and downregulated (n=433) circRNAs, whereaswhile 443 circRNAs were downregulated. GO and KEGG analyses associated differentially expressed circRNAs to neurotransmitters, cell senescence, P53, mTOR, and PI3K-AKT. Microarray sample verification using RT-qPCR confirmed the microarray analysis results on changes in the six circRNAs. Contrary to the microarray analysis, large-sample verification of significantly elevated circRNA expression was partially consistent (hsa_circ_0092270), and inconsistent (hsa_circ_0045808, hsa_circ_0070162), with the microarray results. The findings highlight the significance of circRNAs in AD and that hsa_circ_0092270 represents a promising biomarker for future studies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186929 | GEO | 2022/05/13

REPOSITORIES: GEO

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Project description:Background: There is growing evidence that circular RNAs (circRNAs) play an important role in a variety of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover new circRNAs, investigate their potential role in the pathogenesis of CNI-ED, and construct a circRNA-miRNA-mRNA network. Methods: Twelve male Sprague Dawley rats were randomly divided into bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression profiles of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for real-time polymerase chain reaction (RT-qPCR). The circRNA-miRNA-mRNA network was established using Cytoscape. Gene ontology (GO)-term and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the edgeR package. Results: RNA transcriptome sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR. The ceRNA network contained 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs, including ten circRNAs, six miRNAs, and 227 mRNAs. GO analysis suggested that these ten circRNAs could regulate various processes, such as oxidation-reduction processes, lipid metabolic processes, apoptotic processes, and proteolysis. Furthermore, KEGG analysis of mRNAs in the ceRNA network showed that they were involved in energy metabolism and communication between cells. A protein‐protein interaction network was constructed with the 227 mRNAs, and five hub genes (Ccna2, Cxcl10, Pld1, Mapk11, and Mboat2) were identified. In addition, Using circRNADb, we found 12 circRNAs with protein-coding potential, three of which were highly conserved in humans and rats. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.

Project description:This study compared the circRNA expression levels in plasma samples from patients with IH and control individuals. The circRNA expression profiles were determined using microarray in three pairs of plasma samples from patients with proliferative IH and healthy control individuals. Expression of the identified circRNAs was verified using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and bioinformatic analysis was performed to predict the microRNAs targeted by the validated circRNAs. In the circRNA expression profiles in the plasma of patients with IHs, we found 128 differentially expressed circRNAs, of which 72 were upregulated and 56 were downregulated. The downregulated expression of three circRNAs (hsa_circRNA_101566, hsa_circRNA_103546, and hsa_circRNA_103573) was verified using RT-qPCR. Circular RNAs (circRNAs) are noncoding RNAs that play important roles in tumor progression. Few studies have examined the circRNAs involved in infantile hemangioma (IH) progression. This study compared the circRNA expression levels in plasma samples from patients with IH and control individuals. The circRNA expression profiles were determined using microarray in three pairs of plasma samples from patients with proliferative IH and healthy control individuals. Expression of the identified circRNAs was verified using quantitative reverse transcription polymerase chain reaction (RT-qPCR), and bioinformatic analysis was performed to predict the microRNAs targeted by the validated circRNAs. In the circRNA expression profiles in the plasma of patients with IHs, we found 128 differentially expressed circRNAs, of which 72 were upregulated and 56 were downregulated. The downregulated expression of three circRNAs (hsa_circRNA_101566, hsa_circRNA_103546, and hsa_circRNA_103573) was verified using RT-qPCR. Gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that all identified networks participated in angiogenesis and tumor formation and progression. We found that hsa_circRNA_101566, which can regulate the mammalian target of rapamycin signaling pathway, may be an important regulatory molecule in IH development and that targeting of hsa_miR_520c can indirectly regulate the vascular endothelial growth factor signaling pathway. Further studies are needed to clarify these effects and the underlying mechanisms.

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Differential expression and functional analysis of circular RNA in Alzheimer’s disease

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