scholarly journals Differentially Expressed Circular Non-coding RNAs in Atherosclerotic Aortic Vessels and Their Potential Functions in Endothelial Injury

2021 ◽  
Vol 8 ◽  
Author(s):  
Houwei Li ◽  
Xue Liu ◽  
Na Sun ◽  
Tianshuo Wang ◽  
Jia Zhu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Enrichment Analysis ◽  
Potential Functions ◽  
Endothelial Injury ◽  
Differentially Expressed ◽  
Vascular Endothelial ◽  
Rt Pcr ◽  
Potential Target ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment

Background: Circular non-coding RNA (circRNA) has a variety of biological functions. However, the expression profile and potential effects of circRNA on atherosclerosis (AS) and vascular endothelial injury have not been fully elucidated. This study aims to identify the differentially expressed circRNAs in atherosclerotic aortic vessels and predict their potential functions in endothelial injury.Method: ApoE-/- mice were fed with high-fat diet for 12 weeks to induce AS. Atherosclerotic plaques were evaluated by H&E and Masson staining and immunohistochemistry; differentially expressed circRNAs were detected by Arraystar Circular RNA Microarray and verified by RT-PCR; the potential target mircoRNAs of circRNAs were predicted by miRanda, Tarbase, Targetscan and their expression changes were verified by RT-PCR; the potential target genes of mircoRNAs were predicted by Targetscan and verified by Western blot; the signaling pathways that they might annotate or regulate and their potential functions in vascular endothelial injury were predicted by gene enrichment analysis.Results: Fifty two circRNAs were up-regulated more than twice and 47 circRNAs were down-regulated more than 1.5 times in AS aortic vessels. Mmmu_circRNA_36781 and 37699 were up-regulated both in AS aortic vessels and H2O2-treated mouse aortic endothelial cells (MAECs). The expression of miR-30d-3p and miR-140-3p, the target microRNA of circRNA_37699 and circRNA_36781, were downregulated both in AS vessels and H2O2-treated MAECs. On the contrary, MKK6 and TP53RK, the potential target gene of miR-140-3p and miR-30d-3p, were upregulated both in AS aortic roots and H2O2-treated MAECs. Besides, gene enrichment analysis showed that MAPK and PI3K-AKT signaling pathway were the most potential signaling pathways regulated by the differentially expressed circRNAs in atherosclerosis.Conclusions: Mmu_circRNA_36781 (circRNA ABCA1) and 37699 (circRNA KHDRBS1) were significantly up-regulated in AS aortic vessels and H2O2-treated MAECs. They have potential regulatory effects on atherosclerosis and vascular endothelial injury by targeting miR-30d-3p-TP53RK and miR-140-3p-MKK6 axis and their downstream signaling pathways.

scholarly journals Joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in gastric cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhi Lv ◽  
Liping Sun ◽  
Qian Xu ◽  
Chengzhong Xing ◽  
Yuan Yuan
Keyword(s):  
Gastric Cancer ◽  
Mrna Expression ◽  
Expression Analysis ◽  
Target Genes ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Joint Analysis ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment

Abstract Background N6-methyladenosine (m6A) modification might be closely associated with the genesis and development of gastric cancer (GC). Currently, the evidence established by high-throughput assay for GC-related m6A patterns based on long non-coding RNAs (lncRNAs) remains limited. Here, a joint analysis of lncRNA m6A methylome and lncRNA/mRNA expression profiles in GC was performed to explore the regulatory roles of m6A modification in lncRNAs. Methods Three subjects with primary GC were enrolled in our study and paired sample was randomly selected from GC tissue and adjacent normal tissue for each case. Methylated RNA Immunoprecipitation NextGeneration Sequencing (MeRIP-Seq) and Microarray Gene Expression Profiling was subsequently performed. Then co-expression analysis and gene enrichment analysis were successively conducted. Results After data analysis, we identified 191 differentially m6A-methylated lncRNAs, 240 differentially expressed lncRNAs and 229 differentially expressed mRNAs in GC. Furthermore, four differentially m6A-methylated and expressed lncRNAs (dme-lncRNAs) were discovered including RASAL2-AS1, LINC00910, SNHG7 and LINC01105. Their potential target genes were explored by co-expression analysis. And gene enrichment analysis suggested that they might influence the cellular processes and biological behaviors involved in mitosis and cell cycle. The potential impacts of these targets on GC cells were further validated by CCLE database and literature review. Conclusions Four novel dme-lncRNAs were identified in GC, which might exert regulatory roles on GC cell proliferation. The present study would provide clues for the lncRNA m6A methylation-based research on GC epigenetic etiology and pathogenesis.

scholarly journals Bioinformatics Analysis Predicts ceRNA Regulatory Axes Related to Melanoma Pathogenesis

2021 ◽  
Author(s):  
Lina Liu ◽  
Feng Yang ◽  
Saiyun Lei
Keyword(s):  
Cutaneous Melanoma ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Cerna Network ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment ◽  
Incidence And Mortality ◽  
Malignant Skin ◽  
Clinical Verification ◽  
Geo Database

Abstract Background Melanoma is a highly malignant skin tumour, with an incidence and mortality rates accounting for approximately 5% and >75% of all tumours, respectively. In the present study, we aimed to screen mRNAs, microRNAs, and circRNAs related to the pathogenesis of melanoma via bioinformatics methods. Materials and methods The microarray data correlating with melanoma were obtained from the GEO database, and the differentially expressed genes between melanomatissues and non-melanoma tissues were screened using GEO2R. Moreover, the Hub genes were screened using the STRING database, Cytoscape software, and GEPIA database. The DAVID database was used for gene enrichment analysis. Thereafter, the ceRNA network diagram was constructed using the starBase database and was analysed for survival in order to predict the molecular markers for diagnosis and treatment of skin cutaneous melanoma; the most probable ceRNA mechanism was screened via pan-cancer analysis. Furthermore, the ceRNA network was verified using the GEPIA and UALCAN databases. Results In total, 266, 20, and 10 differentially expressed mRNAs, microRNAs, and circRNA10 were screened. Using Cytoscape software, 59 Hub and 31 key genes were screened, followed by construction of the ceRNA and ceRNA-gene enrichment analysis networks. Conclusion Clinical verification revealed that SIPA1L1 could regulate the expression of DSC3 by sponge adsorption of has-miR-106b and has-miR-20b, and thereby affect the pathogenesis and progression of skin cutaneous melanoma.

Divergent transcriptomic profiles in skeletal muscle of diabetics with and without heart failure

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
N Wood ◽  
CW Cheng ◽  
S Straw ◽  
M Scalabrin ◽  
E Espino-Gonzalez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Pathway Analysis ◽  
Enrichment Analysis ◽  
Left Ventricular Ejection ◽  
Rt Pcr ◽  
Lipid Signalling ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment ◽  
Skeletal Muscle Transcriptome

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with type 2 diabetes mellitus (DM) that have coexistent heart failure (HF) have exacerbated symptoms and prognosis, however beside cardiac dysfunction the mechanisms governing these features are incompletely understood. Evidence indicates abnormalities in the periphery could contribute to this worse clinical phenotype, including a role for skeletal muscle whereby disturbances in the transcriptome could disrupt muscle homeostasis/repair to offer a novel therapeutic approach. Purpose Is the skeletal muscle transcriptome distinguishable between DM patients with and without HF? Methods DM patients without (n = 11) or with HF with reduced left ventricular ejection fraction (LVEF) (n = 16) were included. Muscle biopsies were collected from the pectoralis major during pacemaker implantation. Following RNA extraction and cDNA synthesis, non-bias RNA sequencing (RNAseq) was performed (Cambridge Genomic Services, UK) followed by targeted RT-PCR gene expression of relevant targets. DESeq2 identified differentially expressed genes (DEGs) with a false discovery rate (p < 0.05). Gene enrichment analysis was performed with clusterProfiler v3.16.0 to interrogate the gene ontology database, while pathway analysis was conducted using ReactomePA v1.32.0 to interrogate the Reactome database, using an adjusted p value. Values of p < 0.05 were accepted as significant. Results Groups were not different (p > 0.05) for age (74 ± 11 vs. 66 ± 10 years), BMI (31 ± 7 vs 29 ± 6), sex (n = 2 females per group), or HbA1c (56 ± 10 vs. 57 ± 8 mmol/mol), although LVEF was lower in the group with HF (27 ± 8 vs. 54 ± 2%; p < 0.05).  Of the 19,544 genes analysed, RNAseq identified 53 DEGs between DM patients with and without HF, with several relevant targets related to myofiber homeostasis such as autophagy (RUBCN), protein synthesis (DGKζ), and inflammation/apoptosis (TLE1). Follow-up RT-PCR analysis confirmed a trend towards upregulation of the autophagy-related machinery p62 (p = 0.043) and BNIP3 (p = 0.085) in the HF group, but not ubiquitin-proteasome (MuRF1, MAFbx; p > 0.05). Gene-enrichment analysis of DEGs identified 7 overrepresented terms (P < 0.05), including lipid metabolism/signalling alongside epigenetic modifications related to histone deacetylases (HDAC6/10). Furthermore, pathway analysis identified 4 terms (p < 0.05) related to NOTCH signalling and phosphatidyl inositol-bisphosphate (PIP2) hydrolysis thus indicating alterations to muscle repair and lipid signalling respectively. Conclusion(s): This study confirms that DM patients with and without HF demonstrate distinct skeletal muscle transcriptome profiles. Key differences related to skeletal muscle myogenesis, autophagy, epigenetic regulation, and lipid signalling were identified that could form part of important therapeutic targets. Whether these underlying muscle transcriptome differences contribute to poorer clinical outcomes in DM patients with HF remains to be determined.

scholarly journals AB0005 IDENTIFICATION OF KEY GENES AND PATHWAYS FOR PSORIASIS BASED ON GEO DATABASES BY BIOINFORMATICS ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1037.2-1038
Author(s):  
X. Sun ◽  
S. X. Zhang ◽  
S. Song ◽  
T. Kong ◽  
C. Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Shanxi Province ◽  
Receptor Interaction ◽  
Term Therapy ◽  
Pathway Enrichment Analysis ◽  
Key Genes

Background:Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both, and also has a strong genetic predisposition and autoimmune pathogenic traits1. The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. And it’s also a chronic relapsing disease, which often necessitates a long-term therapy2.Objectives:To investigate the molecular mechanisms of psoriasis and find the potential gene targets for diagnosis and treating psoriasis.Methods:Total 334 gene expression data of patients with psoriasis research (GSE13355 GSE14905 and GSE30999) were obtained from the Gene Expression Omnibus database. After data preprocessing and screening of differentially expressed genes (DEGs) by R software. Online toll Metascape3 was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Interactions of proteins encoded by DEGs were discovered by Protein-protein interaction network (PPI) using STRING online software. Cytoscape software was utilized to visualize PPI and the degree of each DEGs was obtained by analyzing the topological structure of the PPI network.Results:A total of 611 DEGs were found to be differentially expressed in psoriasis. GO analysis revealed that up-regulated DEGs were mostly associated with defense and response to external stimulus while down-regulated DEGs were mostly associated with metabolism and synthesis of lipids. KEGG enrichment analysis suggested they were mainly enriched in IL-17 signaling, Toll-like receptor signaling and PPAR signaling pathways, Cytokine-cytokine receptor interaction and lipid metabolism. In addition, top 9 key genes (CXCL10, OASL, IFIT1, IFIT3, RSAD2, MX1, OAS1, IFI44 and OAS2) were identified through Cytoscape.Conclusion:DEGs of psoriasis may play an essential role in disease development and may be potential pathogeneses of psoriasis.References:[1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31].[2]Zhang YJ, Sun YZ, Gao XH, et al. Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis. Mol Med Rep 2019;20(1):225-35. doi: 10.3892/mmr.2019.10241 [published Online First: 2019/05/23].[3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

scholarly journals Impaired Autophagy Induced by oxLDL/β2GPI/anti-β2GPI Complex through PI3K/AKT/mTOR and eNOS Signaling Pathways Contributes to Endothelial Cell Dysfunction

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Guiting Zhang ◽  
Chao He ◽  
Qianqian Wu ◽  
Guoying Xu ◽  
Ming Kuang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Signaling Pathways ◽  
Western Blotting ◽  
Endothelial Injury ◽  
Vascular Endothelial ◽  
Endothelial Cell Dysfunction ◽  
Western Blotting Analysis ◽  
Cell Dysfunction ◽  
Glycoprotein I

Endothelial cell dysfunction plays a fundamental role in the pathogenesis of atherosclerosis (AS), and endothelial autophagy has protective effects on the development of AS. Our previous study had shown that oxidized low-density lipoprotein/β2-glycoprotein I/anti-β2-glycoprotein I antibody (oxLDL/β2GPI/anti-β2GPI) complex could promote the expressions of inflammatory cytokines and enhance the adhesion of leukocytes to endothelial cells. In the present study, we aimed to assess the effects of oxLDL/β2GPI/anti-β2GPI complex on endothelial autophagy and explore the associated potential mechanisms. Human umbilical vein endothelial cells (HUVECs) and mouse brain endothelial cell line (bEnd.3) were used as models of the vascular endothelial cells. Autophagy was evaluated by examining the expressions of autophagic proteins using western blotting analysis, autophagosome accumulation using transmission electron microscopy, and RFP-GFP-LC3 adenoviral transfection and autophagic flux using lysosome inhibitor chloroquine. The expressions of phospho-PI3K, phospho-AKT, phospho-mTOR, and phospho-eNOS were determined by western blotting analysis. 3-Methyladenine (3-MA) and rapamycin were used to determine the role of autophagy in oxLDL/β2GPI/anti-β2GPI complex-induced endothelial cell dysfunction. We showed that oxLDL/β2GPI/anti-β2GPI complex suppressed the autophagy, evidenced by an increase in p62 protein, a decrease in LC3-II and Beclin1, and a reduction of autophagosome generation in endothelial cells. Moreover, inhibition of autophagy was associated with PI3K/AKT/mTOR and eNOS signaling pathways. Rapamycin attenuated oxLDL/β2GPI/anti-β2GPI complex-induced endothelial inflammation, oxidative stress, and apoptosis, whereas 3-MA alone induced the endothelial injury. Our results suggested that oxLDL/β2GPI/anti-β2GPI complex inhibited endothelial autophagy via PI3K/AKT/mTOR and eNOS signaling pathways and further contributed to endothelial cell dysfunction. Collectively, our findings provided a novel mechanism for vascular endothelial injury in AS patients with an antiphospholipid syndrome (APS) background.

scholarly journals Effect of flapless osteoperforation-assisted tooth movement on atrophic alveolar ridge: Histomorphometric and gene-enrichment analysis

2017 ◽  
Vol 88 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Ji-Won Lee ◽  
Jung-Yul Cha ◽  
Ki-Ho Park ◽  
Yoon-Goo Kang ◽  
Su-Jung Kim
Keyword(s):  
Signaling Pathway ◽  
Tooth Movement ◽  
Osteoclast Differentiation ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Tissue Response ◽  
Alveolar Ridge ◽  
Mineral Density ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment

ABSTRACT Objective: To investigate the effect of flapless osteoperforation on the tissue response of the atrophic alveolar ridge affected by orthodontic tooth movement (OTM). Materials and Methods: An atrophic alveolar ridge model was established in the mandibular quadrants of eight beagle dogs. As a split-mouth design, the quadrants were randomly divided into group C (OTM only) and group OP (OTM with flapless osteoperforation). The rate of OTM for 10 weeks was compared between groups, and micro-CT-based histomorphometric analysis and RNA-sequencing-based gene-enrichment analysis were performed targeting the atrophic ridge. Results: Group OP displayed more rapid tooth movement with lower bone mineral density and higher trabecular fraction in the atrophic ridge than did group C, showing no intergroup difference of total ridge volume. As contributing biological functional pathways in group OP, the genes related to osteoclast differentiation and TNF signaling pathway were up-regulated and those associated with Wnt signaling pathway and AMPK signaling pathway were down-regulated. Conclusions: Flapless osteoperforation facilitated the rate of OTM toward the atrophic ridge, maintaining low bone density, whereas it did not increase the volume of the atrophic ridge.

scholarly journals Positional gene enrichment analysis of gene sets for high-resolution identification of overrepresented chromosomal regions

2008 ◽  
Vol 36 (7) ◽  
pp. e43-e43 ◽  
Author(s):  
K. De Preter ◽  
R. Barriot ◽  
F. Speleman ◽  
J. Vandesompele ◽  
Y. Moreau
Keyword(s):  
High Resolution ◽  
Enrichment Analysis ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment ◽  
Gene Sets

scholarly journals A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xinkui Liu ◽  
Jiarui Wu ◽  
Dan Zhang ◽  
Kaihuan Wang ◽  
Xiaojiao Duan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Network Analysis ◽  
Chinese Herb ◽  
Endocrine System ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment ◽  
Hedyotis Diffusa

Background. As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC) remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW) has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective. The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods. This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results. The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility. Conclusions. This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

scholarly journals Network pharmacology-based elucidation of the molecular mechanism underlying the anti-migraine effect of Asari Radix et Rhizoma

2021 ◽  
Vol 18 (10) ◽  
pp. 2067-2074
Author(s):  
Yun-Bin Jiang ◽  
Mei Zhong ◽  
Ting Huang ◽  
Zhong-Hua Dai ◽  
Xing-Bao Tao ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Scientific Basis ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Hub Genes ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment ◽  
Tnf Gene

Purpose: To determine the molecular mechanism involved in the anti-migraine effect of Asari Radix et Rhizoma (ARR) using network pharmacology. Methods: The compounds present in ARR were identified through information retrieval from literature and public databases, and were screened based on absorption, distribution, metabolism, excretion and toxicity. Target genes related to the selected compounds and migraine were identified or predicted from public databases. Hub genes in ARR against migraine were identified through analysis of interactions in overlapping genes between compounds and migraine target genes, based on STRING database. Gene enrichment analysis of overlapping genes was performed using Database for Annotation, Visualization and Integrated Discovery. Results: A total of 138 compounds were selected as potential bioactive compounds in ARR. Target genes related to the selected compounds (611 genes) and migraine (278 genes) were obtained, including 71 overlapping genes. The hub genes in the anti-migraine effect of ARR were BDNF, IL6, COMT, APP and TNF. Gene enrichment analysis showed the top 10 biological processes or pathways involved in the mechanism of anti-migraine action of ARR. The tissue source of the overlapping genes was not limited to the brain. The results from gene enrichment analysis revealed that the effect of ARR on migraine was holistic, which is characteristic of traditional Chinese medicines. Conclusion: Network pharmacology has been used to decipher the molecular mechanism involved in the action of ARR against migraine. The results provide a scientific basis for the clinical effect of ARR on migraine.

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