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1.
J Mol Neurosci ; 72(3): 468-481, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34580818

RESUMO

Neuropathic pain (NP) involves metabolic processes that are regulated by metabolic genes and their non-coding regulator genes such as microRNAs (miRNAs). Here, we aimed at exploring the key miRNA signatures regulating metabolic genes involved in NP pathogenesis. We downloaded NP-related data from public databases and identified differentially expressed microRNAs (miRNAs) and mRNAs through differential gene expression analysis. The miRNA target prediction was performed, and integration with the differentially expressed metabolic genes (DEMGs) was used for constructing the miRNA-DEMG network. Subsequently, functional enrichment analysis and protein-protein interaction (PPI) analysis were performed to explore the role of DEMGs in the regulatory network. The drug prediction was performed based on the DEMGs in the miRNA-DEMG network. A total of 8251 differentially expressed mRNAs (4193 upregulated and 4058 downregulated), and 959 differentially expressed miRNAs (455 upregulated and 504 downregulated) were identified. Moreover, after target gene prediction, a miRNA-DEMG network composed of 22 miRNAs and 113 mRNAs was constructed. The network was constituted of 135 nodes and 236 edges. We found that DEMGs in the network were mainly enriched in metabolic pathways and metabolic processes. A total of 1200 drugs were predicted as potential therapeutics for NP based on the differentially expressed genes, while 170 drugs were predicted for the DEMGs in the miRNA-DEMG network. Conclusively, our study predicted drugs that may be effective against the metabolic changes induced by miRNA dysregulation in NP. This information will help further reveal the pathological mechanism of NP and provide more treatment options for NP patients.


Assuntos
MicroRNAs , Neuralgia , Biologia Computacional , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
2.
Front Endocrinol (Lausanne) ; 13: 934022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909518

RESUMO

Diabetic nephropathy (DN) is one of the common chronic complications of diabetes with unclear molecular mechanisms, which is associated with end-stage renal disease (ESRD) and chronic kidney disease (CKD). Our study intended to construct a competing endogenous RNA (ceRNA) network via bioinformatics analysis to determine the potential molecular mechanisms of DN pathogenesis. The microarray datasets (GSE30122 and GSE30529) were downloaded from the Gene Expression Omnibus database to find differentially expressed genes (DEGs). GSE51674 and GSE155188 datasets were used to identified the differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), respectively. The DEGs between normal and DN renal tissues were performed using the Linear Models for Microarray (limma) package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal the mechanisms of DEGs in the progression of DN. The protein-protein interactions (PPI) of DEGs were carried out by STRING database. The lncRNA-miRNA-messenger RNA (mRNA) ceRNA network was constructed and visualized via Cytoscape on the basis of the interaction generated through the miRDB and TargetScan databases. A total of 94 significantly upregulated and 14 downregulated mRNAs, 31 upregulated and 121 downregulated miRNAs, and nine upregulated and 81 downregulated lncRNAs were identified. GO and KEGG pathways enriched in several functions and expression pathways, such as inflammatory response, immune response, identical protein binding, nuclear factor kappa b (NF-κB) signaling pathway, and PI3K-Akt signaling pathway. Based on the analysis of the ceRNA network, five differentially expressed lncRNAs (DElncRNAs) (SNHG6, KCNMB2-AS1, LINC00520, DANCR, and PCAT6), five DEmiRNAs (miR-130b-5p, miR-326, miR-374a-3p, miR-577, and miR-944), and five DEmRNAs (PTPRC, CD53, IRF8, IL10RA, and LAPTM5) were demonstrated to be related to the pathogenesis of DN. The hub genes were validated by using receiver operating characteristic curve (ROC) and real-time PCR (RT-PCR). Our research identified hub genes related to the potential mechanism of DN and provided new lncRNA-miRNA-mRNA ceRNA network that contributed to diagnostic and potential therapeutic targets for DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , RNA Longo não Codificante , Biomarcadores , Biologia Computacional , Nefropatias Diabéticas/genética , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
3.
Contrast Media Mol Imaging ; 2022: 1534142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935315

RESUMO

In order to investigate the relationship between inflammation and lncRNA in mixed dry eye disease (DED), this study establishes competitive endogenous RNA (ceRNA) network in mixed DED. Microarray analysis of cornea from mixed DED mice is performed to screen for differences in lncRNA and target genes, and miRNA bioinformatics were predicted based on the ceRNA hypothesis. The ceRNA network, which consists of 96 relationship pairs, is constructed using the top 10 upregulated lncRNAs and all upregulated mRNAs and two pairs of lncRNA-miRNA-mRNA pairs (NONMMUT047964.2-miR-671-5p-Egr-1andNONMMUT054540.2-miR-1934-5p-Grm2) are selected for RT-qRCR verification in mouse corneal epithelial cells under high osmotic pressure and the samples for microarray. Meanwhile, mouse corneal epithelial cell lines (MCECs), transfected siRNA of NONMMUT047964.2 under high osmotic pressure, shows a decrease in apoptosis rate and a decrease in expression of IL-1ß and IL-6. The experimental results show that the NONMMUT047964.2-miR-671-5p-Egr-1 axis may regulate the inflammation and promote the apoptosis of corneal epithelial cells under hypertonic condition.


Assuntos
Síndromes do Olho Seco , MicroRNAs , RNA Longo não Codificante , Animais , Síndromes do Olho Seco/genética , Redes Reguladoras de Genes , Inflamação , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
4.
PLoS One ; 17(8): e0272403, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35913967

RESUMO

Thyroid cancer (TC) is one of the most common thyroid malignancies occurring worldwide, and accounts for about 1% of all the malignant tumors. It is one of the fastest growing tumor and can occur at any age, but it is more common in women. It is important to find the pathogenesis and treatment targets of TC. In this pursuit, the present study was envisaged to investigate the effective carcinogenic biological macromolecules, so as to provide a better understanding of the occurrence and development of TC. The clinical and gene expression data were collected from The Cancer Genome Atlas (TCGA). We clustered mRNA and long non-coding RNA (lncRNA) into different modules by Weighted Gene Co-expression Network Analysis (WGCNA), and calculated the correlation coefficient between the genes and clinical phenotypes. Using WGCNA, we identified the module with the highest correlation coefficient. Subsequently, by using the differential genes expression analysis to screen the differential micro-RNA (miRNA), the univariate Cox proportional hazard regression was employed to screen the hub genes related to overall survival (OS), with P < 0.05 as the statistical significance threshold. Finally, we designed a hub competitive endogenous RNA(ceRNA) network of disease-associated lncRNAs, miRNAs, and mRNAs. From the results of enrichment analysis, the association of these genes could be related to the occurrence and development of TC, and these hub RNAs can be valuable prognostic markers and therapeutic targets in TC.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Glândula Tireoide/genética
5.
J Ovarian Res ; 15(1): 90, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915456

RESUMO

BACKGROUND: Metastasis was the major cause of the high mortality in ovarian cancer. Although some mechanisms of metastasis in ovarian cancer were proposed, few have been targeted in the clinical practice. In the study, we aimed to identify novel genes contributing to metastasis and poor clinical outcome in ovarian cancer from bioinformatics databases. METHODS: Studies collecting matched primary tumors and metastases from ovarian cancer patients were searched in the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened by software R language. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the DEGs were implemented by Metascape. Venn diagram was plotted to present overlapping DEGs. The associations between the overlapping DEGs and prognosis were tested by Cox proportional hazard regression model using a cohort of ovarian cancer patients from the TCGA database. Genes affecting patients' outcomes significantly were served as hub genes. The mechanisms of the hub genes in promoting ovarian cancer metastasis were then predicted by R software. RESULTS: Two gene expression profiles (GSE30587 and GSE73168) met the inclusion criteria and were finally analyzed. A total of 259 genes were significantly differentially expressed in GSE30587, whereas 712 genes were in GSE73168. In GSE30587, DEGs were mainly involved in extracellular matrix (ECM) organization; For GSE73168, most of DEGs showed ion trans-membrane transport activity. There were 9 overlapping genes between the two datasets (RUNX2, FABP4, CLDN20, SVEP1, FAM169A, PGM5, ZFHX4, DCN and TAS2R50). ZFHX4 was proved to be an independent adverse prognostic factor for ovarian cancer patients (HR = 1.44, 95%CI: 1.13-1.83, p = 0.003). Mechanistically, ZFHX4 was positively significantly correlated with epithelial-mesenchymal transition (EMT) markers (r = 0.54, p = 2.59 × 10-29) and ECM-related genes (r = 0.52, p = 2.86 × 10-27). CONCLUSIONS: ZFHX4 might promote metastasis in ovarian cancer by regulating EMT and reprogramming ECM. For clinical applications, ZFHX4 was expected to be a prognostic biomarker for ovarian cancer metastasis.


Assuntos
Biologia Computacional , Neoplasias Ovarianas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Ovarianas/patologia , Fatores de Transcrição/genética
6.
Parasit Vectors ; 15(1): 279, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927758

RESUMO

BACKGROUND: Toxocara canis is a cosmopolitan parasite with a significant adverse impact on the health of humans and animals. The spleen is a major immune organ that plays essential roles in protecting the host against various infections. However, its role in T. canis infection has not received much attention. METHODS: We performed sequencing-based transcriptome profiling of long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression in the spleen of Beagle puppies at 24 h post-infection (hpi), 96 hpi and 36 days post-infection (dpi). Deep sequencing of RNAs isolated from the spleen of six puppies (three infected and three control) at each time point after infection was conducted. RESULTS: Our analysis revealed 614 differentially expressed (DE) lncRNAs and 262 DEmRNAs at 24 hpi; 726 DElncRNAs and 878 DEmRNAs at 96 hpi; and 686 DElncRNAs and 504 DEmRNAs at 36 dpi. Of those, 35 DElncRNA transcripts and 11 DEmRNAs were detected at all three time points post-infection. Many DE genes were enriched in immune response, such as ifit1, ifit2 and rorc. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that some genes (e.g. prkx and tnfrsf11a) were involved in the T cell receptor signaling pathway, calcium signaling pathway, Ras signaling pathway and NF-κB signaling pathway. CONCLUSIONS: The findings of this study show marked alterations in the expression profiles of spleen lncRNAs and mRNAs, with possible implications in the pathophysiology of toxocariasis.


Assuntos
RNA Longo não Codificante , Toxocara canis , Animais , Cães , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Baço/metabolismo , Toxocara canis/genética , Toxocara canis/metabolismo
7.
Drug Des Devel Ther ; 16: 2343-2363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910780

RESUMO

Background: Icariin presents protective effect in several kidney diseases. However, the role of icariin in contrast-induced acute kidney injury (CIAKI) is still unclear. This study aimed to investigate the effect of icariin in CIAKI, as well as exploring the underlying mechanism from the aspect of interaction between protein-coding genes and non-coding RNAs. Methods: The effect of icariin was evaluated in both in vivo and in vitro CIAKI models. Rat kidneys were collected for genome-wide sequencing. The differentially expressed genes (DEGs) were screened and visualized by R software. The function annotation of DEGs was analyzed by Metascape. By Cytoscape software, the competing endogenous RNA (ceRNA) network was constructed, and hub genes were selected. Expressions of hub genes were validated by PCR. Association of hub genes in the ceRNA network and renal function was also examined. Results: Icariin protected against CIAKI in both in vivo and in vitro models. Based on DEGs in icariin pretreated CIAKI rats, lncRNA- and circRNA-associated ceRNA networks were constructed, respectively. Function annotation showed the ceRNA networks were enriched in ERK1 and ERK2 cascade, MAPK signaling and NF-κB signaling. Further, two circRNAs, six lncRNAs, four miRNAs and nine mRNAs were selected as hub genes of the ceRNA network. Among them, eight mRNAs (Acot1, Cbwd1, Ly6i, Map3k14, Mettl2b, Nyap1, Set and Utp20) were negatively correlated with renal function, while one mRNA (Tmem44) was positively correlated with renal function. Conclusion: Icariin presented a protective effect against CIAKI. The ceRNA network, involving Acot1, Cbwd1, Ly6i, Map3k14, Mettl2, Nyap1, Set, Tmem44 and Utp20, might partially contribute to the underlying mechanism of icariin protection by regulation of ERK1 and ERK2 cascade, MAPK signaling and NF-κB signaling.


Assuntos
Injúria Renal Aguda , MicroRNAs , RNA Longo não Codificante , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/prevenção & controle , Animais , Flavonoides , Redes Reguladoras de Genes , MicroRNAs/metabolismo , NF-kappa B/genética , RNA Circular , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Ratos
8.
Sci Rep ; 12(1): 13282, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918429

RESUMO

To better understand the molecular mechanisms of intracranial aneurysm (IA) pathogenesis, we used gene coexpression networks to identify hub genes and functional pathways associated with IA onset. Two Gene Expression Omnibus (GEO) datasets encompassing intracranial aneurysm tissue samples and cerebral artery control samples were included. To discover functional pathways and potential biomarkers, weighted gene coexpression network analysis was employed. Next, single-gene gene set enrichment analysis was employed to investigate the putative biological roles of the chosen genes. We also used receiver operating characteristic analysis to confirm the diagnostic results. Finally, we used a rat model to confirm the hub genes in the module of interest. The module of interest, which was designated the green module and included 115 hub genes, was the key module that was most strongly and negatively associated with IA formation. According to gene set variation analysis results, 15 immune-related pathways were significantly activated in the IA group, whereas 7 metabolic pathways were suppressed. In two GEO datasets, SLC2A12 could distinguish IAs from control samples. Twenty-nine hub genes in the green module might be biomarkers for the occurrence of cerebral aneurysms. SLC2A12 expression was significantly downregulated in both human and rat IA tissue. In the present study, we identified 115 hub genes related to the pathogenesis of IA onset and deduced their potential roles in various molecular pathways; this new information may contribute to the diagnosis and treatment of IAs. By external validation, the SLC2A12 gene may play an important role. The molecular function of SLC2A12 in the process of IA occurrence can be further studied in a rat model.


Assuntos
Aneurisma Intracraniano , Animais , Biomarcadores/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , Aneurisma Intracraniano/metabolismo , Ratos
9.
Biomed Res Int ; 2022: 2114699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924269

RESUMO

Aims: The clinical diagnosis of Kawasaki disease (KD) is not easy because of many atypical manifestations. This study is aimed at finding potential diagnostic markers and therapeutic targets for KD and analysing their correlation with immune cell infiltrations. Methods: First, we downloaded the KD dataset from the Gene Expression Omnibus (GEO) database and used R software to identify differentially expressed genes (DEGs) and perform functional correlation analysis. Then, CIBERSORT algorithm was used to evaluate immune cell infiltrations in samples. Coexpression analysis between DEGs and infiltrating immune cells was performed to screen the main infiltrating immune cells. Subsequently, the least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to screen the core genes related to KD. Finally, correlation analysis between the core genes and the main infiltrating immune cells was performed. Results: 327 DEGs were screened out in this study. Among them, 72 shared genes were the category of genes most likely to be disease-causing for they did not change before and after treatment. After analysis, it was found that expression level of IL2RB in KD tissues was significantly upregulated, the number of resting CD4+ memory T cells was decreased, and the decrease was significantly negatively correlated with the upregulated expression of IL2RB. Therefore, it was speculated that the upregulated expression of IL2RB disrupted Th1/Th2 cell differentiation balance, which led to a decrease of resting CD4+ memory T cells and finally caused disorder of immune microenvironment in patients with KD. Conclusions: Upregulated expression of IL2RB leads to disorder of immune microenvironment in patients with KD and eventually causes the occurrence and development of KD. Therefore, IL2RB may serve as a diagnostic marker and potential therapeutic target for KD.


Assuntos
Redes Reguladoras de Genes , Síndrome de Linfonodos Mucocutâneos , Linfócitos T CD4-Positivos , Perfilação da Expressão Gênica , Humanos , Subunidade beta de Receptor de Interleucina-2/genética , Síndrome de Linfonodos Mucocutâneos/genética
10.
Proc Natl Acad Sci U S A ; 119(33): e2204338119, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35939709

RESUMO

Despite the recent discovery of tissue regeneration enhancers in highly regenerative animals, upstream and downstream genetic programs connected by these enhancers still remain unclear. Here, we performed a genome-wide analysis of enhancers and associated genes in regenerating nephric tubules of Xenopus laevis. Putative enhancers were identified using assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) analyses. Their target genes were predicted based on their proximity to enhancers on genomic DNA and consistency of their transcriptome profiles to ATAC-seq/ChIP-seq profiles of the enhancers. Motif enrichment analysis identified the central role of Krüppel-like factors (Klf) in the enhancer. Klf15, a member of the Klf family, directly binds enhancers and stimulates expression of regenerative genes, including adrenoreceptor alpha 1A (adra1a), whereas inhibition of Klf15 activity results in failure of nephric tubule regeneration. Moreover, pharmacological inhibition of Adra1a-signaling suppresses nephric tubule regeneration, while its activation promotes nephric tubule regeneration and restores organ size. These results indicate that Klf15-dependent adrenergic receptor signaling through regeneration enhancers plays a central role in the genetic network for kidney regeneration.


Assuntos
Elementos Facilitadores Genéticos , Rim , Animais , Cromatina , Elementos Facilitadores Genéticos/genética , Redes Reguladoras de Genes , Rim/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Receptores Adrenérgicos , Regeneração/genética
11.
Math Biosci Eng ; 19(9): 9295-9320, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35942760

RESUMO

WW domain-containing transcription regulator 1 (TAZ, or WWTR1) and Yes-associated protein 1 (YAP) are both important effectors of the Hippo pathway and exhibit different functions. However, few studies have explored their co-regulatory mechanisms in kidney renal clear cell carcinoma (KIRC). Here, we used bioinformatics approaches to evaluate the co-regulatory roles of TAZ/YAP and screen novel biomarkers in KIRC. GSE121689 and GSE146354 were downloaded from the GEO. The limma was applied to identify the differential expression genes (DEGs) and the Venn diagram was utilized to screen co-expressed DEGs. Co-expressed DEGs obtained the corresponding pathways through GO and KEGG analysis. The protein-protein interaction (PPI) network was constructed using STRING. The hub genes were selected applying MCODE and CytoHubba. GSEA was further applied to identify the hub gene-related signaling pathways. The expression, survival, receiver operating character (ROC), and immune infiltration of the hub genes were analyzed by HPA, UALCAN, GEPIA, pROC, and TIMER. A total of 51 DEGs were co-expressed in the two datasets. The KEGG results showed that the enriched pathways were concentrated in the TGF-ß signaling pathway and endocytosis. In the PPI network, the hub genes (STAU2, AGO2, FMR1) were identified by the MCODE and CytoHubba. The GSEA results revealed that the hub genes were correlated with the signaling pathways of metabolism and immunomodulation. We found that STAU2 and FMR1 were weakly expressed in tumors and were negatively associated with the tumor stages. The overall survival (OS) and disease-free survival (DFS) rate of the high-expressed group of FMR1 was greater than that of the low-expressed group. The ROC result exhibited that FMR1 had certainly a predictive ability. The TIMER results indicated that FMR1 was positively correlated to immune cell infiltration. The abovementioned results indicated that TAZ/YAP was involved in the TGF-ß signaling pathway and endocytosis. FMR1 possibly served as an immune-related novel prognostic gene in KIRC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Biologia Computacional/métodos , Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/genética , Proteínas do Tecido Nervoso/metabolismo , Prognóstico , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Fator de Crescimento Transformador beta/metabolismo
12.
Genet Res (Camb) ; 2022: 1415140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35919038

RESUMO

Background: There is still no clear understanding of the pathogenesis of atrial fibrillation (AF). For this purpose, we used integrated analysis to uncover immune infiltration characteristics and investigated their relationship with competing endogenous RNA (ceRNA) network in AF. Methods: Three AF mRNA data sets (GSE14975, GSE79768, and GSE41177) were integrated using the SVA method from Gene Expression Omnibus (GEO). Together with AF circRNA data set (GSE129409) and miRNA data set (GSE70887) from GEO database, we built a ceRNA network. Then hub genes were screened by the Cytoscape plug-in cytoHubba from a protein-protein interaction (PPI) network. As well, CIBERSORT was employed to investigate immune infiltration, followed by Pearson correlation coefficients to unravel the correlation between AF-related infiltrating immune cells and hub genes. Ulteriorly, circRNA-miRNA-mRNA regulatory axises that could be immunologically related to AF were obtained. Results: Ten hub genes were identified from the constructing PPI network. The immune infiltration analysis revealed that the number of monocytes and neutrophils was higher, as well as the number of dendritic cells activated and T cells regulatory (Tregs) was lower in AF. Seven hub genes (C5AR1, CXCR4, HCK, LAPTM5, MPEG1, TLR8, and TNFSF13B) were associated with those 4 immune cells (P < 0.05). We found that the circ_0005299-miR-1246-C5AR1 and circRNA_0079284-miR-623-HCK/CXCR4 regulatory axises may be associated with the immune mechanism of AF. Conclusion: The findings of our study provide insights into immuno-related ceRNA networks as potential molecular regulators of AF progression.


Assuntos
Fibrilação Atrial , MicroRNAs , Fibrilação Atrial/genética , Biologia Computacional/métodos , Redes Reguladoras de Genes/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
13.
Oxid Med Cell Longev ; 2022: 5493051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35915606

RESUMO

Atherosclerosis is a kind of chronic inflammatory cardiovascular disease. Epigenetic regulation plays a crucial role in atherosclerosis. Our study was aimed at finding potential biomarkers associated with the occurrence of atherosclerosis. Two datasets were downloaded from the Gene Expression Omnibus (GEO) database. The epigenome-wide association study (EWAS) analysis was performed on methylation data using CpGassoc package. The differential expression analysis was conducted on mRNA data using limma package. The GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment was done in clusterProfiler package. Finally, the logistic regression model was constructed using generalized linear model (glm) function. Between atherosclerotic vs. nonatherosclerotic samples, totally 4980 cytosine-phosphate-guanine (CpG) sites (annotated to 2860 genes) and 132 differentially expressed genes (DEGs) related to atherosclerosis were identified. The annotated 2860 genes and 132 DEGs were significantly enriched in 9 and 4 KEGG pathways and 289 and 132 GO terms, respectively. After cross-analysis, 6 crucial CpG sites were screened to build the model, including cg01187920, cg03422911, cg08018825, cg10967350, cg14473924, and cg25313204. The diagnostic model could reliably separate the atherosclerosis samples from nonatherosclerotic samples. In conclusion, the 6 CpG sites are probably potential diagnostic biomarkers for atherosclerosis, including cg01187920, cg03422911, cg08018825, cg10967350, cg14473924, and cg25313204.


Assuntos
Aterosclerose , Regulação Neoplásica da Expressão Gênica , Aterosclerose/genética , Biomarcadores , Biologia Computacional , Metilação de DNA/genética , Epigênese Genética , Expressão Gênica , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos
14.
Biomed Res Int ; 2022: 9265088, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928921

RESUMO

Esophageal cancer (ESCA) is a malignant tumor of the upper gastrointestinal tract, with a high mortality rate and poor prognosis. Long noncoding RNAs (lncRNAs) play a role in the malignant progression of tumors by regulating autophagy. This study is aimed at establishing a prognostic model of autophagy-related lncRNAs in ESCA and provide a theoretical basis to determine potential therapeutic targets for ESCA. The transcriptome expression profiles were downloaded from The Cancer Genome Atlas (TCGA). We identified autophagy-related mRNAs and lncRNAs in ESCA using differential expression analysis and the Human Autophagy Database (HADb). Four differentially expressed autophagy-related lncRNAs with a prognostic value were identified using Cox regression and survival analyses. Furthermore, the combination of the selected lncRNAs was able to predict the prognosis of patients with ESCA more accurately than any of the four lncRNAs individually. Finally, we constructed a coexpression network of autophagy-related mRNAs and lncRNAs. This study showed that autophagy-related lncRNAs play an important role in the occurrence and development of ESCA and could become a new target for the diagnosis and treatment of this disease.


Assuntos
Neoplasias Esofágicas , RNA Longo não Codificante , Autofagia/genética , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
BMC Bioinformatics ; 23(1): 330, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945515

RESUMO

BACKGROUND: Biological data suffers from noise that is inherent in the measurements. This is particularly true for time-series gene expression measurements. Nevertheless, in order to to explore cellular dynamics, scientists employ such noisy measurements in predictive and clustering tools. However, noisy data can not only obscure the genes temporal patterns, but applying predictive and clustering tools on noisy data may yield inconsistent, and potentially incorrect, results. RESULTS: To reduce the noise of short-term (< 48 h) time-series expression data, we relied on the three basic temporal patterns of gene expression: waves, impulses and sustained responses. We constrained the estimation of the true signals to these patterns by estimating the parameters of first and second-order Fourier functions and using the nonlinear least-squares trust-region optimization technique. Our approach lowered the noise in at least 85% of synthetic time-series expression data, significantly more than the spline method ([Formula: see text]). When the data contained a higher signal-to-noise ratio, our method allowed downstream network component analyses to calculate consistent and accurate predictions, particularly when the noise variance was high. Conversely, these tools led to erroneous results from untreated noisy data. Our results suggest that at least 5-7 time points are required to efficiently de-noise logarithmic scaled time-series expression data. Investing in sampling additional time points provides little benefit to clustering and prediction accuracy. CONCLUSIONS: Our constrained Fourier de-noising method helps to cluster noisy gene expression and interpret dynamic gene networks more accurately. The benefit of noise reduction is large and can constitute the difference between a successful application and a failing one.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Análise por Conglomerados , Expressão Gênica , Análise dos Mínimos Quadrados
16.
Medicine (Baltimore) ; 101(31): e29555, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35945754

RESUMO

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common forms of head and neck cancers. However, few studies have focused on the correlation between competing endogenous RNA (ceRNAs) and immune cells in LSCC. METHODS: RNAseq expression of LSCC and adjacent tissues were downloaded from The Cancer Genome Atlas to establish a ceRNA network. The key gene in ceRNA was screened by the cox regression analysis to establish a prognostic risk assessment model. The CIBERSORT algorithm was then used to screen important tumor-infiltrating cells related to LSCC. Finally, co-expression analysis was applied to explore the relationship between key genes in the ceRNA network and tumor-infiltrating cells. The external datasets were used to validate critical biomarkers. RESULTS: We constructed a prognostic risk assessment model of key genes in the ceRNA network. As it turned out, Kaplan-Meier survival analysis showed significant differences in overall survival rates between high-risk and low-risk groups (P < .001). The survival rate of the high-risk group was drastically lower than that of the low-risk group, and the AUC of 1 year, 3 years, and 5 years were all above 0.7. In addition, some immune infiltrating cells were also found to be related to LSCC. In the co-expression analysis, there is a negative correlation between plasma cells and TUBB3 (r = -0.33, P = .0013). External dataset validation also supports this result. CONCLUSION: In this study, we found that some key genes (SLC35C1, CLDN23, HOXB7, STC2, TMEM158, TNFRSF4, TUBB3) and immune cells (plasma cells) may correspond to the prognosis of LSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias de Cabeça e Pescoço/genética , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Laríngeas/patologia , Proteínas de Membrana/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteínas Supressoras de Tumor/genética
17.
J Int Med Res ; 50(8): 3000605221113918, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35942560

RESUMO

OBJECTIVE: We aimed to discover potential circulating genes and non-coding molecules (micro RNA [miRNA] and circular RNA [circRNA]) in CD4+ T cells in relation to seasonal allergic rhinitis (SAR). METHODS: Microarray data of GSE50223 were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) during and outside the pollen season were analyzed using R software and by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The protein-protein interactions, modules, miRNAs targeting DEGs, merged miRNA-DEG networks, and circRNAs targeted with miRNAs were further analyzed. RESULTS: We identified 211 DEGs during the pollen season and eight DEGs outside the season, of which only MMP12, NR4A2, and CD69 were differentially expressed both during and outside the pollen season. DEGs during the pollen season were enriched in the GO categories 'neutrophil degranulation', 'neutrophil activation involved in immune response', 'neutrophil mediated immunity', and 'neutrophil activation'. A significant module was identified with key nodes of CDK6 and hsa-miR-29b-3p. Six significant circRNAs were also identified. CONCLUSIONS: Some genes, miRNAs, and circRNAs in CD4+ T may play vital roles in SAR and may thus be potential targets for the prevention and treatment of SAR.


Assuntos
MicroRNAs , Rinite Alérgica Sazonal , Linfócitos T CD4-Positivos/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rinite Alérgica Sazonal/genética , Linfócitos T/metabolismo
18.
NPJ Syst Biol Appl ; 8(1): 28, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948596

RESUMO

According to the recently proposed omnigenic theory, all expressed genes in a relevant tissue are contributing directly or indirectly to the manifestation of complex disorders such as autism. Thus, holistic approaches can be complementary in studying genetics of these complex disorders to focusing on a limited number of candidate genes. Gene interaction networks can be used for holistic studies of the omnigenic nature of autism. We used Louvain clustering on tissue-specific gene interaction networks and their subgraphs exclusively containing autism-related genes to study the effects of peripheral gene interactions. We observed that the autism gene clusters are significantly weaker connected to each other and the peripheral genes in non-neuronal tissues than in brain-related tissues. The biological functions of the brain clusters correlated well with previous findings on autism, such as synaptic signaling, regulation of DNA methylation, or regulation of lymphocyte activation, however, on the other tissues they did not enrich as significantly. Furthermore, ASD subjects with disruptive mutations in specific gene clusters show phenotypical differences compared to other disruptive variants carrying ASD individuals. Our results strengthen the omnigenic theory and can advance our understanding of the genetic background of autism.


Assuntos
Transtorno Autístico , Transtorno Autístico/genética , Metilação de DNA , Epistasia Genética , Redes Reguladoras de Genes/genética , Humanos
19.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 427-438, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35818225

RESUMO

In the recent century, Kidney cancer has emerged as one of the critical renal diseases. Therefore, we analyzed gene expression profiles of non-metastatic kidney cancer to find mechanisms associated with the early-stage pathogenesis of the disease. We concentrated on the most dysregulated genes in expression to discover possible unknown proliferative molecular mechanisms and oncogenic pathways promoting kidney renal cancer growth. Survival analysis, expression profiling, and gene set over-representation analysis were conducted on the most upregulated and most down-regulated genes alongside the hub genes. Our results demonstrated that pathways engaged in the metabolism of amino acids and carbohydrates and those involved in peroxisome organization were shown to be important in developing benign tumors. Furthermore, upregulation of genes such as CXCL9 and 10 genes and CXCR4 in chemokine response pathways would bolster differentiation and engagement of immune cells in the tumor microenvironment. C3, one of the essential members of the complement system, with a high degree and betweenness centrality in the PPI network, upregulated significantly not only in our analysis but also in the validation expression profiling results and survival analysis. We also identified genes such as TYROBP, ITGB2, and EGFR to be engaged in both immunological pathways and superoxide pathways. Furthermore, we found that downregulation of Aldolase B engaged in Glycolysis and Gluconeogenesis pathways would help develop benign tumors. Finally, many top hub genes, including TYMS, PTPRC, AURKA, FN1, UBE2C, and CD53 were proposed to be engaged in the progression of non-metastatic renal tumors. This holistic interrogation calls attention to investigate further and experimentally validate the proposed molecular mechanisms.


Assuntos
Redes Reguladoras de Genes , Neoplasias Renais , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Mapas de Interação de Proteínas/genética , Microambiente Tumoral
20.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 405-420, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35818227

RESUMO

Sepsis has been recognized to be a life-threatening organ dysfunction caused by the dysregulation of the host response to infections. Our work aims to screen key biomarkers related to neutrophils in sepsis using bioinformatics analysis. For this purpose, the microarray datasets related to neutrophils in sepsis patients were downloaded from the Gene Expression Omnibus (GEO) database. According to the Bayesian test, the Limma package in R was used to screen differentially expressed genes (DEGs). Then, DEGs were uploaded to the DAVID online diagnostic tool for subsequent Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment on the selected DEGs. Next, protein-protein interaction (PPI) network was established based on the selected DEGs using the STRING website and the Cytoscape software. Furthermore, according to the function of the iRegulon plug-in in Cytoscape, our study further predicts and established regulatory networks related to transcription factors and regulatory genes. In addition, the miRWalk2.0 database was used to search for miRNA-DEG pairs, associated with the conduction of intersections of miRNAs predicted by TargetScan, Miranda, miRDB and RNA22 databases. Then, these miRNA-DEG pairs were also displayed in the form of a regulatory network through Cytoscape. Finally, two datasets were selected to verify the screened genes, regulatory factors, and miRNAs, to plot receiver operating characteristics (ROC) curves and compute the area under the curve (AUC) values. The results showed that AKT1, MMP9, ARG1, ETS1 targeting AKT1, and has-miR-124-3p targeting RPS6KA5 may have diagnostic value for patients with sepsis and septic shock. While further experimental studies are required to confirm their role in septic neutrophils.


Assuntos
MicroRNAs , Sepse , Teorema de Bayes , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Neutrófilos , Mapas de Interação de Proteínas/genética , Sepse/genética , Fatores de Transcrição/genética
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