scholarly journals Identifying Pivotal microRNAs and Target Genes Associated With the Pathogenesis of Atrial Fibrillation

2020 ◽  
Author(s):  
Shengjue Xiao ◽  
Yufei Zhou ◽  
Qiaozhi Liu ◽  
Tiantian Zhang ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Signaling Pathway ◽  
Target Genes ◽  
Heat Shock Protein 90 ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Expression Array ◽  
Class B ◽  
Transcription Factor Target ◽  
Limma Package

Abstract Background: Atrial fibrillation (AF) is the most common arrhythmia. However, specific molecular mechanism of AF remains unclear. Our study aimed to identify pivotal target genes and miRNAs in the process of AF, which help provide the basis for clinical diagnosis and the methods for early intervention. Methods: Three gene expression array datasets (GSE31821, GSE41177 and GSE79768) and a miRNA expression array dataset of AF dataset (GSE68475) were downloaded. Differential expressed genes (DEGs) were identified using the LIMMA package and differential expressed miRNAs (DEMs) were screened from GSE68475. Target genes of DEMs were predicted using the miRTarbase database, the number of the intersection between DEGs and these target genes was 26, named CDEGs. The common DEGs (CDEGs) was subject to following analysis. Results: A total of 264 DEGs and 40 DEMs were identified between the AF and control groups. Functional and pathway enrichment analyses of up-regulated DEGs and down-regulated DEGs were performed. The CDEGs were mainly enriched in PI3K-Akt signaling pathway, negative regulation of cell division and response to hypoxia. Subsequently, the protein-protein interaction (PPI) network, the microRNA‐transcription factor‐target regulatory network and drug‐gene network were also constructed by Cytoscape software. Conclusion: The present study revealed several novel genes and miRNAs involved in AF. We speculated that PI3K-Akt signaling pathway might participate in the pathogenesis of AF with the interaction of MYC proto-oncogene (MYC), heat shock protein 90 kDA alpha, class B, member 1 (HSP90AB1) and DNA damage-inducible transcript 4 (DDIT4), moreover, SOD2 (superoxide dismutase 2) could target miR-671-5p, miR-4306, miR-3125, miR-4298 in the progression of AF.

scholarly journals Identification of Pivotal MicroRNAs and Target Genes Associated with Persistent Atrial Fibrillation Based on Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shengjue Xiao ◽  
Yufei Zhou ◽  
Qiaozhi Liu ◽  
TianTian Zhang ◽  
Defeng Pan
Keyword(s):  
Atrial Fibrillation ◽  
Regulatory Network ◽  
Gene Network ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Expression Array ◽  
Transcription Factor Target

Atrial fibrillation (AF) is one of the most common supraventricular arrhythmias worldwide. However, the specific molecular mechanism underlying AF remains unclear. Our study is aimed at identifying pivotal microRNAs (miRNAs) and targeting genes associated with persistent AF (pAF) using bioinformatics analysis. Three gene expression array datasets (GSE31821, GSE41177, and GSE79768) and an miRNA expression array dataset (GSE68475) associated with pAF were downloaded. Differentially expressed genes (DEGs) were identified using the LIMMA package, and differentially expressed miRNAs (DEMs) were screened from GSE68475. Target genes for DEMs were predicted using the miRTarBase database, and intersections between these target genes and DEGs were selected for further analysis, including the generation of protein–protein interaction (PPI) network, miRNA–transcription factor–target regulatory network, and drug–gene network. A total of 264 DEGs and 40 DEMs were identified between the pAF and control groups. Functional and pathway enrichment analyses of up- and downregulated DEGs were performed. The common genes (CGs) were primarily enriched in the phosphoinositide 3-kinase- (PI3K-) protein kinase B (Akt) signaling pathway, negative regulation of cell division, and response to hypoxia. The PPI network, miRNA–transcription factor–target regulatory network, and drug–gene network were constructed using Cytoscape. The present study revealed several novel miRNAs and genes involved in pAF. We speculated that miR-4298, miR-3125, miR-4306, and miR-671-5p could represent significant miRNAs that act on the target gene superoxide dismutase 2 (SOD2) during the development of pAF and may serve as essential biomarkers for pAF diagnosis and treatment. Moreover, MYC might function in pAF pathogenesis through the PI3K–Akt signaling pathway.

scholarly journals Analysis of microRNA Expression after Glutamine Intervention in Acute Renal Ischemia-Reperfusion Injury

2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Suhua Li ◽  
Xuan Huang ◽  
Shun Wang ◽  
Xueqian Chu ◽  
Munire Aierken
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Kidney Tissue ◽  
Akt Signaling ◽  
Protective Mechanism ◽  
Renal Tubules ◽  
Akt Signaling Pathway

Background. Ischemia-reperfusion acute kidney injury (I/R AKI) is a severe kidney disease with high mortality and morbidity. This study aimed to explore the protective mechanism of glutamine (GLN) against I/R AKI. Methods.The I/R AKI rat model was established, and HE staining of kidney tissue and serum creatinine (SCr) and blood urea nitrogen (BUN) detection were performed. The miRNAs were sequenced by high throughput in rat kidney tissue samples. Differentially expressed miRNAs (DEmiRs) between the I/R group and I/R + GLN group were screened, and enrichment analysis for target genes of DEmiRs was performed. Meanwhile, human HK-2 cells were cultured, and an I/R model was established to verify the expression of DEmiRs. Results. Compared with the I/R group, the SCr and BUN levels at each time point were lower in the I/R + GLN group. Vacuolar degeneration of renal tubules in the I/R + GLN group was significantly reduced. In the 104 DEmiRs, we selected miR-132-5p, miR-205, and miR-615 as key miRNAs. KEGG analysis showed that the Notch signaling pathway, PI3K-Akt signaling pathway, and cGMP signaling pathway were mainly related to the GLN against I/R. qRT-PCR verified the downregulation of miR-205 in the I/R group, compared to the sham and I/R + GLN group. The I/R model was established with HK-2 cells, and the expression of miR-132-5p and miR-205 was decreased. Conclusion. GLN reduced I/R-induced AKI. There were significant differences between miRNAs expression in I/R after GLN treatment. The process of GLN against I/R-induced AKI may be related to the Notch and PI3K-Akt signaling pathway.

Identification and Functional Analysis of Serum Specific MiRNAs in Patients with Recurrent Aphthous Somatitis of Excess-heat or Yin-deficiency Syndrome

2019 ◽  
Author(s):  
Jie Bao ◽  
Zhengyang Zhu ◽  
Xizhao Zhang ◽  
Lin Huang ◽  
Li Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Deficiency Syndrome ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Excess Heat ◽  
Yin Deficiency ◽  
Heat Syndrome

Abstract Background. MiRNAs has become an important regulator in many processes. The purpose of our study is to screen the key serum miRNAs of different syndrome of recurrent aphthous stomatitis (RAS), to find new biomarkers for the diagnosis of RAS and to further explore their role in the pathogenesis of RAS.Method. Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat or yin-deficiency syndrome and healthy individuals. Core miRNAs were then identified under miRNA microarray analyses. Target prediction and bioinformatic analyses were carried out and gene-pathway-networks were visualized to better understand the relationship between different genes and pathways.Result. (1) 90 individuals meeting the inclusion criteria were collected in this study, of which 30 were normal control, 30 were patients of excess-heat syndrome and the rest were patients of yin-deficiency syndrome. Among them, 9 miRNAs were screened out in excess-heat syndrome group, with 1 upregulated and 8 downregulated. And four random miRNAs (hsa-miR-20b-5p, hsa-miR-122-5p, hsa-miR-483-5p and hsa-miR-3197) were validated by real-time PCR method. 14 miRNAs were screened out in yin-deficiency syndrome group (7 upregulated and 7 downregulated). And hsa-miR-17-5p, hsa-miR-106-5p and hsa-miR-20b-5p were validated. (2) A total of 4776 target genes were identified for the validated 9 miRNAs in excess-heat syndrome group. These targets were enriched in GO categories including nervous system development, homophilic cell adhesion via plasma membrane adhesion molecules, and calcium ion binding and KEGG pathway such as proteoglycans in cancer, P13K-AKT signaling pathway and Calcium signaling pathway. 10172 target genes were identified for the validated 14 miRNAs in yin-deficiency syndrome group. The enriched GO categories included protein binding, positive regulation of transcription from RNA polymerase II promoter and membrane and enriched KEGG pathway included pathways in cancer, MAPK signaling pathway and Ras signaling pathway .Conclusion. Hsa-miR-20b-5p in patients with RAS could act as the novel biomarker for clinical diagnosis of the disease. It is upregulated in RAS patients of excess-heat syndrome while downregulated in patients of yin-deficiency syndrome. The PI3K-Akt signaling pathway and MAPK signaling pathway and related target genes may provide new insights into the molecular mechanisms of excess-heat syndrome and yin-deficiency syndrome RAS, respectively.

scholarly journals Transcriptome analysis reveals that long noncoding RNAs contribute to developmental differences between medium-sized ovarian follicles of Meishan and Duroc sows

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengxun Li ◽  
Yi Liu ◽  
Su Xie ◽  
Lipeng Ma ◽  
Zhichao Zhao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Litter Size ◽  
Target Genes ◽  
Hormone Secretion ◽  
Follicular Development ◽  
Akt Signaling ◽  
Developmental Differences ◽  
Differentially Expressed ◽  
Akt Signaling Pathway ◽  
Potential Target

AbstractOvulation rate is an extremely important factor affecting litter size in sows. It differs greatly among pig breeds with different genetic backgrounds. Long non-coding RNAs (lncRNAs) can regulate follicle development, granulosa cell growth, and hormone secretion, which in turn can affect sow litter size. In this study, we identified 3554 lncRNAs and 25,491 mRNAs in M2 follicles of Meishan and Duroc sows. The lncRNA sequence and open reading frame lengths were shorter than mRNAs, and lncRNAs had fewer exons, were less abundant, and more conserved than protein-coding RNAs. Furthermore, 201 lncRNAs were differentially expressed (DE) between breeds, and quantitative trait loci analysis of DE lncRNAs were performed. A total of 127 DE lncRNAs were identified in 119 reproduction trait-related loci. In addition, the potential target genes of lncRNAs in cis or trans configurations were predicted. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that some potential target genes were involved in follicular development and hormone secretion-related biological processes or pathways, such as progesterone biosynthetic process, estrogen metabolic process, ovarian steroidogenesis, and PI3K-Akt signaling pathway. Furthermore, we also screened 19 differentially expressed lncRNAs in the PI3K-Akt signaling pathway as candidates. This study provides new insights into the roles of lncRNAs in follicular growth and development in pigs.

scholarly journals Potential prognostic value of hsa-miR-18a in hepatocellular carcinoma and the underlying key down-stream gene CHRM2: a comprehensive bioinformatic analysis*

2021 ◽  
Author(s):  
Zile Fu ◽  
Shuzhan Wen ◽  
Tianchang Wei ◽  
Ruiqi Gu ◽  
Shuying Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Survival Analysis ◽  
Signaling Pathway ◽  
Target Genes ◽  
Differential Expression Analysis ◽  
Bioinformatic Analysis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Pubmed Database

Abstract Background Hepatocellular carcinoma (HCC) is still the fourth leading cause of cancer-related death. Better prognosticators are warranted for HCC. Hsa-miR-18a has been considered implicated in the pathogenesis of several tumors including HCC. Methods Bioinformatic analyses were conducted to predict target genes and carry out enrichment analysis. Validated downstream genes of hsa-miR-18a were obtained from PubMed database. Differential expression analysis was conducted within the “edgeR” R package based on the TCGA datasets. Survival analysis was performed by Kaplan-Meier survival analysis. All the visualizations were implemented by R. Results Bioinformatic analysis obtained a total of 90 target genes of hsa-miR-18a and revealed that target genes were involved in pathways essential for cancer onset and development such as cell cycle and PI3K/AKT signaling pathway. A review of literatures found target genes of miR-18a indeed participating in the biological processes of HCC. CHRM2 was identified as a special gene after the intersection analysis of TCGA differentially expressed genes (DEGs) and predicted target genes. Survival analysis validated that hsa-miR-18a and CHRM2 significantly affected the prognosis of HCC patients. Conclusion There is a strong association between hsa-miR-18a with tumors including HCC via participating essential tumor-promoting pathways including cell cycle, PI3K/AKT signaling pathway, etc. Furthermore, high miR-18a expression and low CHRM2 expression could lead to a poor prognosis in HCC. In conclusion, miR-18a could serve as an expectational prognostic biomarker in HCC.

scholarly journals Identifying mechanisms of Epimedii Folium against Alzheimer’s disease via a network pharmacology approach Epimedii Folium treats Alzheimer’s disease via PI3K-AKT

2021 ◽  
Vol 19 ◽  
pp. 205873922110414
Author(s):  
Yan Zhao ◽  
Guangmei Liu ◽  
Yang Yang ◽  
Ling Chen ◽  
Ying Shang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Target Therapy ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Pathway Gene

To elucidate the mechanism of the multi-target action of Epimedii Folium on Alzheimer’s disease, this study focuses on the analysis of network pharmacology. Based on a bioinformatics approach, this study obtained the effective components of Epimedium through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, predicted the compound targets through the Pharmapper and Swiss target prediction database and then through Gene Expression Omnibus Datasets and Therapeutic Target Database. We collected and analysed of heral and disease targets, constructed the network. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology enrichment, then the key targets and pathways of Epimedii Folium to cope with Alzheimer’s disease have been identified. Twenty-three bioactive components and 477 potential target genes of Epimedii Folium were identified. A total of 1612 target diseases were identified. Through network module analysis, 30 hub target genes were identified. Through enrichment analysis of the KEGG pathway, hub target genes were largely enriched in the PI3K-AKT signaling pathway. Through the analysis of network pharmacology, it was found that Epimedii Folium might play the role of multi-compound and multi-target therapy through the PI3K-AKT signaling pathway. These findings provide helpful directions for future clinical studies.

scholarly journals Identification and Functional Analysis of Serum Specific MiRNAs in Recurrent Aphthous Somatitis Patients With Excess-heat or Yin-deficiency

2020 ◽  
Author(s):  
Jie Bao ◽  
Zhengyang Zhu ◽  
Xizhao Zhang ◽  
Lin Huang ◽  
Li Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Deficiency Syndrome ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Akt Signaling Pathway ◽  
Excess Heat ◽  
Yin Deficiency ◽  
Heat Syndrome

Abstract Background:To identity key miRNAs as signatures for recurrent aphthous stomatitis(RAS)with Excess-heat or Yin-deficiency bymiRNA microarrays. Method: Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat oryin-deficiencysyndrome and healthy individuals. CoremicroRNAs (miRNAs) were then identified under miRNA microarray analyses. Target prediction and bioinformatic analyses were carried out andgene-pathway-networks werevisualized to better understand the relationship between differentgenes and pathways.Result:(1) 90 individuals meeting the inclusion criteria were collected in this study, of which 30 were normal control, 30 were patients of excess-heat syndrome and the rest were patients ofyin-deficiency syndrome. Among them, 9 miRNAs werescreened out in excess-heat syndrome group, with 1 upregulated and 8 downregulated. And four randommiRNAs(hsa-miR-20b-5p, hsa-miR-122-5p, hsa-miR-483-5p and hsa-miR-3197) were validatedby real-time PCR method. 14 miRNAs werescreened out in yin-deficiency syndrome group(7 upregulated and 7 downregulated). And hsa-miR-17-5p, hsa-miR-106-5p and hsa-miR-20b-5p were validated. (2)A total of 4776 target genes were identified for the validated 9 miRNAs in excess-heat syndrome group.These targets were enriched inGO categories including nervous system development, homophilic cell adhesion via plasma membrane adhesion molecules, and calcium ion binding and KEGG pathway such as proteoglycans in cancer, P13K-AKT signaling pathway and Calcium signaling pathway. 10172 target genes were identified for the validated 14 miRNAs in yin-deficiency syndrome group. The enrichedGO categories included protein binding, positive regulation of transcription from RNA polymerase II promoter and membrane andenrichedKEGG pathway included pathways in cancer, MAPK signaling pathway and Ras signaling pathway.Conclusion:Hsa-miR-20b-5p in patients with RAS could act as the novel target for syndromeclassification of the disease. It is upregulated in RAS patients with excess-heat syndrome while downregulated in patients with yin-deficiency syndrome. The PI3K-Akt signaling pathway and MAPK signaling pathway and related target genes may provide new insights into the molecular mechanisms of RAS with excess-heat syndrome or yin-deficiency syndrome, respectively.

Bioinformatics Analysis of a Regulatory lncRNA–miRNA–mRNA Network and Signaling Pathways in Patients With Cardiomyopathy

2021 ◽  
Author(s):  
Tao Chen ◽  
Yu-Yao Liu ◽  
Shu-Jun Li ◽  
Hong Che ◽  
Sheng-Lin Ge
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Kinase Inhibitor ◽  
Biological Effects ◽  
Akt Signaling ◽  
Differentially Expressed ◽  
Control Group ◽  
Messenger Rnas ◽  
Akt Signaling Pathway ◽  
Original Dataset

Abstract Background:Cardiomyopathy is a disease with a very low cure rate and a very complex pathogenesis.Although genes are known to play an important role in various types of cardiomyopathy, the specific mechanism has not been well studied.Methods:We screened the GSE29819 dataset from the Gene Expression Omnibus database (GEO) for long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) with significant differences using R software. microRNAs (miRNAs) regulated by the lncRNAs were retrieved from the miRcode database. The downstream target genes of the miRNAs were predicted by miRDB, miRTarBase, and TargetScan, and genes consistent with the original dataset were selected to construct a lncRNA–miRNA–mRNA network. Finally, the biological effects of these genes were studied by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.Results: 223 differentially expressed genes and 13 differentially expressed lncRNAs has been screened in the cardiomyopathy tissues.After database screening and matching, the final lncRNA–miRNA–mRNA network included three lncRNAs, eight miRNAs, and nine mRNAs. These nine genes are mainly involved in the prolactin signaling pathway, EGFR tyrosine kinase inhibitor resistance, toxoplasmosis, the chemokine signaling pathway, and the PI3K–Akt signaling pathway. In the PI3K–Akt signaling pathway, the expression levels of these genes are significantly upregulated compared with the control group, and the main genes involved in regulation are JAK2/DDIT4/FOXO3. JAK2 and FOXO3 play an important regulatory role in the PI3K–Akt signaling pathway.Conclusion:The AC017002–miRNA-590-5p–FOXO3 network may be involved in the pathogenesis of cardiomyopathy, which will enable the determination of new markers to predict cardiomyopathy, and thus reduce the risk of developing the disease.

scholarly journals MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jian Xu ◽  
Mingqiang Sun ◽  
Xiaodong Li ◽  
Lei Huang ◽  
Zhenzhong Gao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hippocampal Neurons ◽  
Target Genes ◽  
Expression Profiles ◽  
Neuronal Cell ◽  
Febrile Seizures ◽  
Akt Signaling ◽  
Akt Signaling Pathway

AbstractFebrile seizures (FSs) are common neurological disorders in both infants and children, although the precise underlying mechanism remains to be explored, especially in the expression pattern and function of microRNAs (miRNAs). In this report, we aimed to screen new potential miRNAs and examine the role of miR-148a-3p in hippocampal neurons in FS rats via Synaptojanin-1 (SYNJ1). Thirty rats were randomly divided into the normal and FS model groups, which were investigated by miRNA array. This process identified 31 differentially expressed (20 upregulated and 11 downregulated) miRNAs and potential miRNA target genes. In addition, hippocampal neurons were assigned into five groups for different transfections. Apoptosis was detected by TUNEL and flow cytometry. SYNJ1 was identified as a target gene of miR-148-3p. In vitro experiments revealed that inhibition of miR-148a-3p decreased neuronal cell apoptosis. Moreover, overexpression of miR-148a-3p resulted in activation of PI3K/Akt signaling pathway and the apoptosis of hippocampal neurons. MiR-148a-3p inhibitor could reverse the above events. Taken together, our data demonstrated that the hippocampal miRNA expression profiles of a rat model of FS provide a large database of candidate miRNAs and neuron-related target genes. Furthermore, miR-148a-3p acted as a apoptosis enhcaner via the activation of the SYNJ1/PI3K/Akt signaling pathway, highlighting a potential therapeutic target in the treatment of infants with hyperthermia-induced brain injury.

Sign in / Sign up

Export Citation Format

Share Document