scholarly journals Identification of biomarkers and pathways in hypertensive nephropathy based on the ceRNA regulatory network

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhen Wang ◽  
Zhongjie Liu ◽  
Yingxia Yang ◽  
Lei Kang

Abstract Background Hypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life. The purpose of this study was to identify the potential biomarkers of HTN and understand its possible mechanisms. Methods The dataset numbered GSE28260 related to hypertensive and normotensive was downloaded from NCBI Gene Expression Omnibus. Then, the differentially expressed RNAs (DERs) were screened using R limma package, and functional analyses of DE-mRNA were performed by DAVID. Afterwards, a ceRNA network was established and KEGG pathway was analyzed based on the Gene Set Enrichment Analysis (GSEA) database. Finally, a ceRNA regulatory network directly associated with HTN was proposed. Results A total of 947 DERs were identified, including 900 DE-mRNAs, 20 DE-lncRNAs and 27 DE-miRNAs. Based on these DE-mRNAs, they were involved in biological processes such as fatty acid beta-oxidation, IRE1-mediated unfolded protein response, and transmembrane transport, and many KEGG pathways like glycine, serine and threonine metabolism, carbon metabolism. Subsequently, lncRNAs KCTD21-AS1, LINC00470 and SNHG14 were found to be hub nodes in the ceRNA regulatory network. KEGG analysis showed that insulin signaling pathway, glycine, serine and threonine metabolism, pathways in cancer, lysosome, and apoptosis was associated with hypertensive. Finally, insulin signaling pathway was screened to directly associate with HTN and was regulated by mRNAs PPP1R3C, PPKAR2B and AKT3, miRNA has-miR-107, and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG. Conclusions Insulin signaling pathway was directly associated with HTN, and miRNA has-miR-107 and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG were the biomarkers of HTN. These results would improve our understanding of the occurrence and development of HTN.

2019 ◽  
Author(s):  
lei kang ◽  
Zhen Wang ◽  
Zhongjie Liu ◽  
Yingxia Liu

Abstract Background Hypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life. The purpose of this study was to identify the potential biomarkers of HTN and understand its possible mechanisms.Methods The dataset numbered GSE28260 related to hypertensive and normotensive was downloaded from NCBI Gene Expression Omnibus. Then, the differentially expressed RNAs (DERs) were screened using R limma package, and functional analyses of DE-mRNA were performed by DAVID. Afterwards, a ceRNA network was established and KEGG pathway was analyzed based on the Gene Set Enrichment Analysis (GSEA) database. Finally, a ceRNA regulatory network directly associated with HTN was proposed.Results A total of 947 DERs were identified, including 900 DE-mRNAs, 20 DE-lncRNAs and 27 DE-miRNAs. Based on these DE-mRNAs, they were involved in biological processes such as fatty acid beta-oxidation, IRE1-mediated unfolded protein response, and transmembrane transport, and many KEGG pathways like glycine, serine and threonine metabolism, carbon metabolism. Subsequently, lncRNAs KCTD21-AS1, LINC00470 and SNHG14 were found to be hub nodes in the ceRNA regulatory network. KEGG analysis showed that insulin signaling pathway, glycine, serine and threonine metabolism, pathways in cancer, lysosome, and apoptosis was associated with hypertensive. Finally, insulin signaling pathway was screened to directly associate with HTN and was regulated by mRNAs PPP1R3C, PPKAR2B and AKT3, miRNA has-miR-107, and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG.Conclusions Insulin signaling pathway was directly associated with HTN, and miRNA has-miR-107 and lncRNAs SNHG14, TUG1, ZNF252P-AS1 and MIR503HG were the biomarkers of HTN. These results would improve our understanding of the occurrence and development of HTN.


2020 ◽  
Author(s):  
Zhen Wang ◽  
Zhongjie Liu ◽  
Yingxia Liu ◽  
Lei Kang

Abstract Background Hypertensive nephropathy (HTN) is a kind of renal injury caused by chronic hypertension, which seriously affect people’s life. The purpose of this study was to identify the potential biomarkers of HTN and understand its possible mechanisms. Methods The dataset numbered GSE28260 related to hypertensive and normotensive was downloaded from NCBI Gene Expression Omnibus. Then, the differentially expressed RNAs (DERs) were screened using R limma package, and functional analyses of DE-mRNA were performed by DAVID. Afterwards, a ceRNA network was established and KEGG pathway was analyzed based on the Gene Set Enrichment Analysis (GSEA) database. Finally, a ceRNA regulatory network directly associated with HTN was proposed. Results A total of 947 DERs were identified, including 900 DE-mRNAs, 20 DE-lncRNAs and 27 DE-miRNAs. Based on these DE-mRNAs, they were involved in biological processes such as fatty acid beta-oxidation, IRE1-mediated unfolded protein response, and transmembrane transport, and many KEGG pathways like glycine, serine and threonine metabolism, carbon metabolism. Subsequently, lncRNAs KCTD21-AS1 , LINC00470 and SNHG14 were found to be hub nodes in the ceRNA regulatory network. KEGG analysis showed that insulin signaling pathway, glycine, serine and threonine metabolism, pathways in cancer, lysosome, and apoptosis was associated with hypertensive. Finally, insulin signaling pathway was screened to directly associate with HTN and was regulated by mRNAs PPP1R3C , PPKAR2B and AKT3 , miRNA has-miR-107, and lncRNAs SNHG14 , TUG1 , ZNF252P-AS1 and MIR503HG . Conclusions Insulin signaling pathway was directly associated with HTN, and miRNA has-miR-107 and lncRNAs SNHG14 , TUG1 , ZNF252P-AS1 and MIR503HG were the biomarkers of HTN. These results would improve our understanding of the occurrence and development of HTN.


Author(s):  
Dan Hao ◽  
Xiao Wang ◽  
Xiaogang Wang ◽  
Bo Thomsen ◽  
Kaixing Qu ◽  
...  

Background: Resveratrol (RSV), a phenolic compound, is present in many human dietary sources, such as peanuts, peanut butter, grapes skin, and grape wine. RSV has been widely known for its benefits on human health. Beef from cattle skeletal muscle is one of the main sources of protein for human consumption. Previous studies have also found that pork and chicken qualities are influenced by the feed supplementation with RSV. In addition, our previous study demonstrated the RSV effects on bovine myoblast differentiation using messenger RNA (mRNA) data. In this study, we mainly focused on the influences of RSV on microRNA (miRNA) expression. Method: We used 20 μM RSV to treat primary bovine myoblasts and extracted RNA for miRNA sequencing. After quality control and alignment for clean reads, we conducted quantification and analysis of differentially expressed (DE) miRNAs in the case (RSV-treated) group versus control (non-RSV treated) group. Next, we predicted the target genes for the DE miRNAs and analyzed them for the enrichments of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results: Finally, we identified 93 DE miRNAs (adjusted P-value < 0.05), of them 44 were upregulated and 49 were downregulated. Bta-miR-34c was the most significantly upregulated miRNA. In silico, prediction results indicated 1,869 target genes for the 93 DE miRNAs. GO enrichment analysis for the genes targeted by DE miRNAs revealed two significant GO terms (adjusted P-value < 0.05), in which the most significant one was stereocilium (GO:0032420). KEGG enrichment analysis showed five significant pathways, and the top significant KEGG pathway was the insulin signaling pathway (bta04910) (adjusted P-value < 0.05). Conclusions: This study provided an improved understanding of effects of RSV on primary bovine myoblast differentiation through the miRNA modulations. The results suggested that RSV could promote differentiation of primary bovine myoblast by stimulating the miRNA expressions. The target genes of DE miRNAs were significantly enriched in the insulin signaling pathway, thus potentially contributing to improving muscle leanness by increasing the energy metabolism.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zijian Xiao ◽  
Qing Ye ◽  
Xiaomei Duan ◽  
Tao Xiang

Hyperinflammation is related to the development of COVID-19. Resveratrol is considered an anti-inflammatory and antiviral agent. Herein, we used a network pharmacological approach and bioinformatic gene analysis to explore the pharmacological mechanism of Resveratrol in COVID-19 therapy. Potential targets of Resveratrol were obtained from public databases. SARS-CoV-2 differentially expressed genes (DEGs) were screened out via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE147507, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; then, protein-protein interaction network was constructed. The common targets, GO terms, and KEGG pathways of Resveratrol targets and SARS-CoV-2 DEGs were confirmed. KEGG Mapper queried the location of common targets in the key pathways. A notable overlap of the GO terms and KEGG pathways between Resveratrol targets and SARS-CoV-2 DEGs was revealed. The shared targets between Resveratrol targets and SARS-CoV-2 mainly involved the IL-17 signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Our study uncovered that Resveratrol is a promising therapeutic candidate for COVID-19 and we also revealed the probable key targets and pathways involved. Ultimately, we bring forward new insights and encourage more studies on Resveratol to benefit COVID-19 patients.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2268
Author(s):  
Dina Medina-Vera ◽  
Juan Antonio Navarro ◽  
Rubén Tovar ◽  
Cristina Rosell-Valle ◽  
Alfonso Gutiérrez-Adan ◽  
...  

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.


2021 ◽  
Author(s):  
Longhua Feng ◽  
Pengjiang Cheng ◽  
Zhengyun Feng ◽  
Xiaoyu Zhang

Abstract Background: To investigate the role of transmembrane p24 trafficking protein 2 (TMED2) in lung adenocarcinoma (LUAD) and determine whether TMED2 knockdown could inhibit LUAD in vitro and in vivo.Methods: TIMER2.0, Kaplan-Meier plotter, gene set enrichment analysis (GSEA), Target Gene, and pan-cancer systems were used to predict the potential function of TMED2. Western blotting and immunohistochemistry were performed to analyze TMED2 expression in different tissues or cell lines. The proliferation, development, and apoptosis of LUAD were observed using a lentivirus-mediated TMED2 knockdown. Bioinformatics and western blot analysis of TMED2 against inflammation via the TLR4/NF-κB signaling pathway were conducted. Results: TMED2 expression in LUAD tumor tissues was higher than that in normal tissues and positively correlated with poor survival in lung cancer and negatively correlated with apoptosis in LUAD. The expression of TMED2 was higher in tumors or HCC827 cells. TMED2 knockdown inhibited LUAD development in vitro and in vivo and increased the levels of inflammatory factors via the TLR4/NF-κB signaling pathway. TMED2 was correlated with TME, immune score, TME-associated immune cells, their target markers, and some mechanisms and pathways, as determined using the TIMER2.0, GO, and KEGG assays.Conclusions: TMED2 may regulate inflammation in LUAD through the TLR4/NF-κB signaling pathway, and enhance the proliferation, development, and prognosis of LUAD by regulating inflammation, which provide a new strategy for treating LUAD by regulating inflammation.


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