scholarly journals Circular RNA detection identifies circPSEN1 alterations in brain specific to Autosomal Dominant Alzheimer Disease

2021 ◽  
Author(s):  
Hsiang-Han Chen ◽  
Abdallah Eteleeb ◽  
Ciyang Wang ◽  
Maria Victoria Fernandez ◽  
John P. Budde ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
In Silico ◽  
Autosomal Dominant ◽  
Age At Onset ◽  
Wnt Signaling Pathway ◽  
Circular Rna ◽  
Circular Rnas ◽  
Mutation Carriers ◽  
Functional Analyses

Background: Autosomal-dominant Alzheimer's disease (ADAD) is caused by pathogenic mutations in APP, PSEN1, and PSEN2, which usually lead to an early age at onset (<65). Circular RNAs are a family of non-coding RNAs highly expressed in the nervous system and especially in synapses. We aimed to investigate differences in brain gene expression of linear and circular transcripts from the three ADAD genes in controls, sporadic AD, and ADAD. Methods: We obtained and sequenced RNA from brain cortex using standard protocols. Linear counts were obtained using the TOPMed pipeline; circular counts, using python package DCC. After stringent quality control (QC), we obtained the counts for PSEN1, PSEN2 and APP genes. Only circPSEN1 passed QC. We used DESeq2 to compare the counts across groups, correcting for biological and technical variables. Finally, we performed in-silico functional analyses using the Circular RNA interactome website and DIANA mirPath software. Results: Our results show significant differences in gene counts of circPSEN1 in ADAD individuals, when compared to sporadic AD and controls (ADAD=22, AD=274, Controls=25 - ADADvsCO: log2FC=0.786, p=9.08x10-05, ADADvsAD: log2FC=0.576, p=2.00x10-03). The high gene counts are contributed by two circPSEN1 species (hsa_circ_0008521 and hsa_circ_0003848). No significant differences were observed in linear PSEN1 gene expression between cases and controls, indicating that this finding is specific to the circular forms. In addition, the high circPSEN1 levels do not seem to be specific to PSEN1 mutation carriers; the counts are also elevated in APP and PSEN2 mutation carriers. In-silico functional analyses suggest that circPSEN1 is involved in several pathways such as axon guidance (p=3.39x10-07), hippo signaling pathway (p=7.38x10-07), lysine degradation (p=2.48x10-05) or Wnt signaling pathway (p=5.58x10-04) among other KEGG pathways. Additionally, circPSEN1 counts were able to discriminate ADAD from sporadic AD and controls with an AUC above 0.70. Conclusions: Our findings show the differential expression of circPSEN1 is increased in ADAD. Given the biological function previously ascribed to circular RNAs and the results of our in-silico analyses, we hypothesize that this finding might be related to neuroinflammatory events that lead or that are caused by the accumulation of amyloid-beta.

scholarly journals Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Fatemeh Khodabandehloo ◽  
Sara Taleahmad ◽  
Reza Aflatoonian ◽  
Farzad Rajaei ◽  
Zahra Zandieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Hub Genes ◽  
Gene Expressions ◽  
Cell Based Therapy ◽  
Wnt Pathways ◽  
Key Pathways

Abstract Background Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0. Results Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE. Conclusions These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.

scholarly journals Expression Profiling and Functional Analysis of Circular RNAs in Inner Mongolian Cashmere Goat Hair Follicles

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangzheng Shang ◽  
Yu Wang ◽  
Rong Ma ◽  
Zhengyang Di ◽  
Zhihong Wu ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathway ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Expression Profiles ◽  
Circular Rna ◽  
Hair Follicles ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cashmere Goats

BackgroundInner Mongolian cashmere goats have hair of excellent quality and high economic value, and the skin hair follicle traits of cashmere goats have a direct and important effect on cashmere yield and quality. Circular RNA has been studied in a variety of tissues and cells.ResultIn this study, high-throughput sequencing was used to obtain the expression profiles of circular RNA (circRNA) in the hair follicles of Inner Mongolian cashmere goats at different embryonic stages (45, 55, 65, and 75 days). A total of 21,784 circRNAs were identified. At the same time, the differentially expressed circRNA in the six comparison groups formed in the four stages were: d75vsd45, 59 upregulated and 33 downregulated DE circRNAs; d75vsd55, 61 upregulated and 102 downregulated DE circRNAs; d75vsd65, 32 upregulated and 33 downregulated DE circRNAs; d65vsd55, 67 upregulated and 169 downregulated DE circRNAs; d65vsd45, 96 upregulated and 63 downregulated DE circRNAs; and d55vsd45, 76 upregulated and 42 downregulated DE circRNAs. Six DE circRNA were randomly selected to verify the reliability of the sequencing results by quantitative RT-PCR. Subsequently, the circRNA corresponding host genes were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The results showed that the biological processes related to hair follicle growth and development enriched by GO mainly included hair follicle morphogenesis and cell development, and the signaling pathways related to hair follicle development included the Notch signaling pathway and NF-κB signaling pathway. We combined the DE circRNA of d75vsd45 with miRNA and mRNA databases (unpublished) to construct the regulatory network of circRNA–miRNA–mRNA, and formed a total of 102 pairs of circRNA–miRNA and 126 pairs of miRNA–mRNA interactions. The binding relationship of circRNA3236–chi-miR-27b-3p and circRNA3236–chi-miR-16b-3p was further verified by dual-luciferase reporter assays, and the results showed that circRNA3236 and chi-miR-27b-3p, and circRNA3236 and chi-miR-16b-3p have a targeted binding relationship.ConclusionTo summarize, we established the expression profiling of circRNA in the fetal skin hair follicles of cashmere goats, and found that the host gene of circRNA may be involved in the development of hair follicles of cashmere goats. The regulatory network of circRNA–miRNA–mRNA was constructed and preliminarily verified using DE circRNAs.

scholarly journals Identifying Main Genes and Pathways by Using Gene Expression Profiling in Primary Immunodeficiency HOIL-1/RBCK1 Disorder Patients

2021 ◽  
Author(s):  
Khyber Shinwari ◽  
Guojun Liu ◽  
Mikhail Bolkov ◽  
Monib Ullah ◽  
Irina Tuzankina
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Signaling Pathway ◽  
Focal Adhesion ◽  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Wnt Signaling Pathway ◽  
Negative Regulation ◽  
Coagulation Cascade ◽  
Bacterial Disease

HOIL-1/RBCK1 deficiency is a new autosomal receiving disorder with dysfunctional cellular responses to pro-inflammatory cytokines, leading to auto-inflammation, pyogenic bacterial disease, and muscle amylopectinosis growth. Our study with integrated bioinformatics studies of the feature genes and the correlative gene functions, investigated the molecular mechanisms of RBCK1 deficiency. GSE31064 dataset expression profile was downloaded from the Omnibus Gene Expression database. Between RBCK1, MYDK88, NEMO deficient fibroblast, and healthy fibroblast specimens, differentially expressed genes (DEGs) were defined. Gene ontology (GO) gene role enrichment analysis and the Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed using the Annotation, Visualization and Integrated Discovery Database (DAVID). The protein-protein interaction (PPI) of these DEGs was visualized using Cytoscape. GO analysis revealed that the “Skeletal system development, Extracellular matrix organization, Positive regulation of cell migration, Negative regulation of canonical Wnt signaling pathway, Cell adhesion, Angiogenesis and Negative regulation of BMP signaling pathway, Serine-type carboxypeptidase activity, Polysaccharide binding, Calcium ion binding, frizzled binding, Neuropilin binding, and cell adhesion molecule binding, extracellular exosome, extracellular space, extracellular region, lysosomal lumen, endoplasmic reticulum lumen, cell surface and focal adhesion to BP, MF, and CC, respectively. The study of the KEGG pathway showed that the complement and coagulation cascade, interactions of the ECM receptor, PI3K-Akt signaling pathway, PPAR signaling pathway, TGF-beta signaling pathway, cancer pathway, viral carcinogenesis and focal adhesion pathway were closely correlated with the incidence of RBCK1 deficiency. Importantly, it has been predicted that TK1, AURKB, CDCA2, UBE2C, KIFC1, CEP55, CDCA3, GINS2, MCM6 and CDC45 are significantly associated with RCBK1 deficiency. Our study offers a record of damaged genes and pathways in RCBK1, which will boost the understanding of RBCK1 deficiency pathogenesis and other inherent immunodeficiency diseases. This research has the potential and can possibly use in the clinic for diagnosis and targeted therapy of HOIL-1/RBCK1 disorder and other inherent immunodeficiencies.

scholarly journals Disease duration in autosomal dominant familial Alzheimer disease

2020 ◽  
Vol 6 (5) ◽  
pp. e507
Author(s):  
Ivanna M. Pavisic ◽  
Jennifer M. Nicholas ◽  
Antoinette O'Connor ◽  
Helen Rice ◽  
Kirsty Lu ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Survival Time ◽  
Disease Duration ◽  
Autosomal Dominant ◽  
Age At Onset ◽  
Survival Models ◽  
Research Centre ◽  
Mutation Carriers ◽  
Familial Alzheimer Disease ◽  
Atypical Presentations

ObjectiveTo use survival modeling to estimate disease duration in autosomal dominant familial Alzheimer disease (ADAD) and ascertain whether factors influencing age at onset also affect survival.MethodsSymptomatic mutation carriers (201 presenilin 1 [PSEN1] and 55 amyloid precursor protein [APP]) from ADAD families referred to the Dementia Research Centre, between 1987 and 2019, were included. Survival was assessed with respect to age at onset, year of birth, APOE ε4 status, cognitive presentation, and sex using multilevel mixed-effects Weibull survival models. The contribution of mutation and family to variance in age at onset and duration was also assessed.ResultsEstimated mean survival was 11.6 (10.4–12.9) years and was similar for APP and PSEN1 mutations. Sixty-seven percent of the variance in age at onset was explained by mutation and 72% by mutation and family together. In contrast, only 6% of the variance in disease duration was explained by mutation specificity and 18% by family membership. Irrespective of gene, survival appeared longer for successive generations and in individuals with atypical presentations. Older age at onset was associated with longer duration within PSEN1 and shorter duration within APP mutation carriers. No differences in survival time were found between sexes or between mutations located before or beyond codon 200 within PSEN1.ConclusionsSurvival is influenced by mutation to a much lesser extent than age at onset. Survival time has increased over time and is longer in atypical presentations. These insights may inform the interpretation of disease-modifying therapy trials in ADAD.

Computationally Design of Inhibitory Peptides Against Wnt Signaling Pathway: In Silico Insight on Complex of DKK1 and LRP6

2017 ◽  
Vol 24 (1) ◽  
pp. 49-60 ◽  
Author(s):  
Elham Rismani ◽  
Hamzeh Rahimi ◽  
Seyed Shahriar Arab ◽  
Kayhan Azadmanesh ◽  
Morteza Karimipoor ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
In Silico ◽  
Wnt Signaling Pathway ◽  
Inhibitory Peptides

Circular RNA as a potential diagnostic and/or therapeutic target for endometriosis

2020 ◽  
Vol 14 (13) ◽  
pp. 1277-1287
Author(s):  
Parisa M Dana ◽  
Mona Taghavipour ◽  
Hamed Mirzaei ◽  
Bahman Yousefi ◽  
Bahram Moazzami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Therapeutic Target ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Circular Rnas ◽  
Biological Functions ◽  
Parental Gene

Endometriosis is a pathology form of endometrium that behaves in a similar way to malignancies, such as invasion and resistance to apoptosis. Circular RNAs (CircRNAs) are a class of noncoding RNAs that have several biological functions including, miRNA sponging, sequestering of proteins, enhancing parental gene expression and translation resulting in polypeptides. In this review, we highlighted the roles of circRNAs as potential diagnostic and therapeutic biomarkers in endometriosis. Moreover, we summarized the roles of circRNAs in the pathogenesis of endometriosis via different signaling pathways, such as the miRNA network and apoptosis.

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