scholarly journals Bioinformatical Analysis of miRNA-mRNA Interaction Network Underlying Macrophage Aging and Cholesterol-Responsive Difference between Young and Aged Macrophages

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jianqing Li ◽  
Xue Yin ◽  
Bingyu Zhang ◽  
Chen Li ◽  
Peirong Lu
Keyword(s):  
Target Genes ◽  
Density Lipoprotein ◽  
Interaction Network ◽  
Metabolic Process ◽  
Cholesterol Homeostasis ◽  
Age Related Macular Degeneration ◽  
Differentially Expressed ◽  
Functional Annotations ◽  
Age Related ◽  
Bioinformatical Analysis

Purpose. Macrophage aging is involved with the occurrence and progression of age-related macular degeneration (AMD). The purpose of this study was to identify the specific microRNAs (miRNA), mRNAs, and their interactions underlying macrophage aging and response to cholesterol through bioinformatical analysis in order to get a better understanding of the mechanism of AMD. Methods. The microarray data were obtained from Gene Expression Omnibus (accession GSE111304 and GSE111382). The age-related differentially expressed genes in macrophages were identified using R software. Further miRNA-mRNA interactions were analyzed through miRWalk, mirTarBase, starBase, and then produced by Cytoscape. The functional annotations including Gene Ontology and KEGG pathways of the miRNA target genes were performed by the DAVID and the STRING database. In addition, protein-protein interaction network was constructed to identify the key genes in response to exogenous cholesterol. Results. When comparing aged and young macrophages, a total of 14 miRNAs and 101 mRNAs were detected as differentially expressed. Besides, 19 validated and 544 predicted miRNA-mRNA interactions were detected. Lipid metabolic process was found to be associated with macrophage aging through functional annotations of the miRNA targets. After being treated with oxidized and acetylated low-density lipoprotein, miR-714 and 16 mRNAs differentially expressed in response to both kinds of cholesterol between aged and young macrophages. Among them, 6 miRNA-mRNA predicted pairs were detected. The functional annotations were mainly related to lipid metabolism process and farnesyl diphosphate farnesyl transferase 1 (FDFT1) was identified to be the key gene in the difference of response to cholesterol between aged and young macrophages. Conclusions. Lipid metabolic process was critical in both macrophage aging and response to cholesterol thus was regarded to be associated with the occurrence and progression of AMD. Moreover, miR-714-FDFT1 may modulate cholesterol homeostasis in aged macrophages and have the potential to be a novel therapeutic target for AMD.

scholarly journals The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1593
Author(s):  
Leonor Jacobo-Albavera ◽  
Mayra Domínguez-Pérez ◽  
Diana Jhoseline Medina-Leyte ◽  
Antonia González-Garrido ◽  
Teresa Villarreal-Molina
Keyword(s):  
Plasma Membrane ◽  
Cancer Progression ◽  
Transmembrane Protein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Age Related Macular Degeneration ◽  
Phospholipid Content ◽  
Atp Binding ◽  
Age Related ◽  
Atp Binding Cassette

Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases. This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression.

scholarly journals Integrative Analyses of Genes and miRNAs Associated With Age-Related Sarcopenia

2021 ◽  
Author(s):  
Sangyeob Lee ◽  
Jun-Il Yoo
Keyword(s):  
Target Genes ◽  
Expression Profiles ◽  
Vastus Lateralis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Analysis Tool ◽  
Age Related ◽  
Differentially Expressed Mirnas ◽  
Low Expression

Abstract Background: Sarcopenia is an age-related disease with skeletal muscle loss, weakness, and functional impairment. The potential causes of sarcopenia including the programmed cell death of muscles, inflammation, reactive oxygen species, protein turnover, and mitochondrial dysfunction have been studied. The purpose of this study was to find differentially expressed miRNAs (DE-miRNAs) in the muscle samples of older people (GSE23527). In addition, we performed to identify new miRNA-mRNA regulatory network for treating sarcopeniaMethods: Gene expression profiles were obtained from microarray datasets (GSE8479 and GSE1428) of the vastus lateralis muscles of young and older male subjects. Dataset GSE23527 was derived from the platform of GPL10358 (LC_MRA-1001_miRHuman_11.0_080411) and contained microRNA arrays of 12 young muscle samples and 12 older muscle samples. The DEGs between the older and young GSE8479 and GSE1428 samples were identified using the online analysis tool imaGEO (https://imageo.genyo.es). Pathway and process enrichment analysis with the ontology sources in the KEGG pathway, GO biological processes, Reactome gene sets, WikiPathways, and CORUM were analyzed by Metascape. A PPI (protein-protein interaction) network of DEGs was constructed using the Search Tool for Retrieval of Interacting Genes (STRING) app in Cytoscape software (version 1.6.0). GEO2R (https://www.ncbi.nlm.nih.gov) was used to select differentially expressed miRNAs (DE-miRNAs) in the GSE 23527 dataset.Results: In the GSE8479 and GSE1428 datasets, a total of 81 DEGs were discovered, including four upregulated genes and 77 downregulated genes. The top 12 clusters and their representative enriched terms were identified using Metascape. A total of 79 nodes and 186 edges were predicted in the PPI network. One upregulated DE-miRNA (hsa-miR-450a-5p) and six downregulated DE-miRNAs (hsa-miR-127-3p, hsa-miR-24-2-5p, hsa-miR-378a-5p, hsa-miR-532-5p, hsa-miR-487b-5p, and has-miR-487b-3p) were selected in the miRBase database. The MiRWalk online database was utilized for exploring 8017 genes that were selected as genes regulated by DE-miRNAs and six of them overlapped with hub genes. COX7A1 and NDUFB5 showed significantly low expression in sarcopenia patients compared to the controls. COX7B and PDHA1 also displayed low expression in sarcopenia patients, but expression of COX7A1 and NDUFB5 was not significant. TIMM8A and CS showed similar expression rates in both samples.Conclusions: The present bioinformatics analysis showed that two target genes (COX7A1 and NDUFB5) were potentially downregulated in sarcopenia patients. These two genes could be the cause of sarcopenia with aging. In addition, present study showed that several miRNAs (hsa-miR-378a-5p, hsa-miR-532-5p, hsa-miR-127-3p, and hsa-miR-24-2-5p) were identified as regulating the target genes. These results suggest that controlling the identified miRNAs could be a prospective strategy for treating sarcopenia by regulating the mRNA-miRNA network.

Bioinformatics Analysis Reveals Functions of MicroRNAs in Rice Under the Drought Stress

2021 ◽  
Vol 15 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Yan Peng ◽  
Yuewu Liu ◽  
Xinbo Chen
Keyword(s):  
Drought Stress ◽  
Target Genes ◽  
Hot Spot ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Promising Tool ◽  
Differentially Expressed Mirnas ◽  
Aba Biosynthesis

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identified. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.

Clofibrate causes an upregulation of PPAR-α target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs

2007 ◽  
Vol 293 (1) ◽  
pp. R70-R77 ◽  
Author(s):  
Sebastian Luci ◽  
Beatrice Giemsa ◽  
Holger Kluge ◽  
Klaus Eder
Keyword(s):  
Adipose Tissue ◽  
Target Genes ◽  
Regulatory Element ◽  
Control Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Expression

This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-α and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-α target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs ( P < 0.05). mRNA concentrations of sterol regulatory element-binding proteins (SREBP)-1 and -2, insulin-induced genes ( Insig) -1 and Insig-2, and the SREBP target genes acetyl-CoA carboxylase, 3-methyl-3-hydroxyglutaryl-CoA reductase, and low-density lipoprotein receptor in liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-α in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-α activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs.

Elevated apolipoprotein A1 and HDL cholesterol associated with age-related macular degeneration: two population cohorts

2021 ◽  
Author(s):  
Liv Tybjærg Nordestgaard ◽  
Anne Tybjærg-Hansen ◽  
Ruth Frikke-Schmidt ◽  
Børge Grønne Nordestgaard
Keyword(s):  
Macular Degeneration ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Age Related Macular Degeneration ◽  
Apolipoprotein A1 ◽  
Age Related ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Plasma Apolipoprotein

Abstract Context To enable prevention and treatment of age-related macular degeneration(AMD), understanding risk factors for AMD is important. Objective We tested the hypotheses that elevated plasma apolipoprotein A1 and high-density lipoprotein(HDL) cholesterol, and low levels of low-density lipoprotein(LDL) cholesterol, are associated with increased risk of AMD. Design and Setting From the Danish general population, we studied 106,703 and 16,032 individuals in the Copenhagen General Population Study(CGPS) and the Copenhagen City Heart Study(CCHS) with median follow-up of respectively 9 and 32 years. Main Outcome Measures 1,787 AMD in CGPS and 206 in CCHS. Results Higher concentrations of plasma apolipoprotein A1 and HDL cholesterol, and lower concentrations of LDL cholesterol, were associated with higher risk of AMD in CGPS. After multifactorial adjustment, individuals in the highest versus lowest quartile of plasma apolipoprotein A1 and HDL cholesterol had hazard ratios for AMD of 1.40(95%CI:1.20-1.63) and 1.22(1.03-1.45). Corresponding hazard ratios for individuals in the lowest versus highest quartile of LDL cholesterol were 1.18(1.02-1.37). Per 100 mg/dL higher plasma apolipoprotein A1, 1 mmol/L(39 mg/dL) higher HDL, and 1 mmol/L(39mmol/L) lower LDL cholesterol, the hazard ratios for AMD were 1.53(1.31-1.80), 1.19(1.07-1.32), and 1.05(1.00-1.11), respectively, with similar results across strata of different risk factors. Higher concentrations of HDL cholesterol were also associated with higher risk of AMD in the CCHS. Conclusion Elevated plasma apolipoprotein A1 and HDL cholesterol, and lower LDL cholesterol, are associated with increased risk of age-related macular degeneration.

The effects of eight serum lipid biomarkers on age-related macular degeneration risk: a Mendelian randomization study

2020 ◽  
Author(s):  
Xikun Han ◽  
Jue-Sheng Ong ◽  
Alex W Hewitt ◽  
Puya Gharahkhani ◽  
Stuart MacGregor
Keyword(s):  
Macular Degeneration ◽  
Serum Lipid ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lipid Biomarkers ◽  
Age Related Macular Degeneration ◽  
Apolipoprotein A1 ◽  
Lipoprotein Cholesterol ◽  
European Descent ◽  
Age Related

Abstract Background Age-related macular degeneration (AMD) is a leading cause of vision loss. Whereas lipids have been studied extensively to understand their effects on cardiovascular diseases, their relationship with AMD remains unclear. Methods Two-sample Mendelian randomization (MR) analyses were performed to systematically evaluate the causal relationships between eight serum lipid biomarkers, consisting of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], triglycerides (TG) and non-HDL cholesterol (non-HDL-C), and the risk of different AMD stages and subtypes. We derived 64–407 genetic instruments for eight serum lipid biomarkers in 419 649 participants of European descent from the UK Biobank cohort. We conducted genome-wide association studies (GWAS) for 12 711 advanced AMD cases [8544 choroidal neovascularization (CNV) and 2656 geographic atrophy (GA) specific AMD subtypes] and 5336 intermediate AMD cases with 14 590 controls of European descent from the International AMD Genomics Consortium. Results Higher genetically predicted HDL-C and ApoA1 levels increased the risk of all AMD subtypes. LDL-C, ApoB, CHOL and non-HDL-C levels were associated with decreased risk of intermediate and GA AMD but not with CNV. Genetically predicted TG levels were associated with decreased risk of different AMD subtypes. Sensitivity analyses revealed no evidence for directional pleiotropy effects. In our multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results. Conclusion These results suggest the role of lipid metabolism in drusen formation and particularly in AMD development at the early and intermediate stages. Mechanistic studies are warranted to investigate the utility of lipid pathways for therapeutic treatment in preventing AMD.

scholarly journals Bioinformatic Analysis of Circular RNA-Associated ceRNA Network Associated with Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jiacheng Wu ◽  
Shui Liu ◽  
Yien Xiang ◽  
Xianzhi Qu ◽  
Yingjun Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Pathway Analysis ◽  
Target Genes ◽  
Kegg Pathway ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Differentially Expressed ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Kegg Pathway Analysis

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910–miR-1261–UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.

scholarly journals System Analysis of MIRNAs in Maize Internode Elongation

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 417
Author(s):  
Chuanxi Peng ◽  
Xing Wang ◽  
Tianyu Feng ◽  
Rui He ◽  
Mingcai Zhang ◽  
...  
Keyword(s):  
Target Genes ◽  
System Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Internode Elongation ◽  
Differentially Expressed Mirnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.

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