The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes

Purpose. Previous studies have investigated the transcriptional modulations of aldosterone overproduction of aldosterone-producing adenomas (APAs). We aimed to systematically study the genes and pathways associated with molecular mechanism underlying APA by bioinformatics analysis and experimental validation for the expression profile. Methods. This study was performed based on three gene expression profiles (GSE64957, GSE8514, and GSE60042). Differentially expressed gene (DEG) investigation, function and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed by the bioinformatics analysis. For the validation with quantitative PCR, tissues from 11 patients with nonfunctioning adrenal adenoma (NFA) and 13 with APA were included in our cohort. Results. In this study, the bioinformatics analysis was performed and 182 upregulated and 88 downregulated DEGs were identified. As expected, the upregulated DEGs were primarily involved in calcium ion homeostasis ( p = 2.00X10−4). In the KEGG pathway analysis, calcium signaling pathway ( p = 4.38X10−6) and the aldosterone synthesis and secretion ( p = 8.73X10−6) were enriched. Moreover, quantitative PCR was performed to detect the expression of 7 upregulated genes (PCP4, ATP2A3, CYP11B2, CLCN5, HTR4, VDR, and AQP2) among the intersection of DEGs. The mRNA levels of CYP11B2, HTR4, and AQP2 were significantly increased in APA samples compared to NFA (24.420 folds of NFA, p < 0.001; 3.753 folds of NFA, p = 0.002; and 11.487 folds of NFA, p = 0.018). Conclusion. In summary, the present study showed several candidate genes with high expression from bioinformatics analysis and our cohort. Also, the DEGs were enriched in aldosterone synthesis and secretion and calcium signaling pathway as expected.

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The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes

10.21203/rs.3.rs-466199/v1 ◽

2021 ◽

Author(s):

Yinjie Gao ◽

Xiaosen Ma ◽

Huiping Wang ◽

Yunying Cui ◽

Yushi Zhang ◽

...

Keyword(s):

Calcium Signaling ◽

Signaling Pathway ◽

Quantitative Pcr ◽

Bioinformatics Analysis ◽

Expression Profiles ◽

Ion Homeostasis ◽

Differentially Expressed Gene ◽

Differentially Expressed ◽

Mrna Levels ◽

Calcium Signaling Pathway

Abstract BackgroundPrevious studies have investigated the transcriptional modulations of aldosterone overproduction of aldosterone-producing adenomas (APAs), and several potential genes were found with high expressions. PurposeWe aimed to systematically study the genes and pathways associated with molecular mechanism underlying APA by bioinformatics analysis and experimental validation for the expression profile. MethodsThis study was performed based on three gene expression profiles (GSE64957, GSE8514, and GSE60042). Differentially expressed gene (DEG) investigation, function and pathway enrichment, as well as protein-protein interaction (PPI) network, were performed by the bioinformatics analysis. For the validation with quantitative PCR, tissues from 11 patients with non-functioning adrenal adenoma (NFA) and 13 with APA were included in our cohort. ResultsIn this study, the bioinformatics analysis was performed and 182 upregulated and 88 downregulated DEGs were identified. As expected, the upregulated DEGs were primarily involved in calcium ion homeostasis (GO: 0055074, n = 3, p = 2.00X10-4). In the KEGG pathway analysis, calcium signaling pathway (hsa04020, n = 8, p= 4.38X10-6) and the aldosterone synthesis and secretion (hsa04925, n = 6, p = 8.73X10-6) were enriched. Moreover, quantitative PCR was performed to detect the expression of 7 upregulated genes (PCP4, ATP2A3, CYP11B2, CLCN5, HTR4, VDR and AQP2) among the intersection of DEGs. The mRNA levels of CYP11B2, HTR4 and AQP2 were significantly increased in APA samples compared to NFA (24.420 folds of NFA, p<0.001, 3.753 folds of NFA, p=0.002 and 11.487 folds of NFA, p=0.018).ConclusionIn summary, the present study showed several candidate genes with high expression from bioinformatics analysis and our cohort. And the DEGs were enriched in aldosterone synthesis and secretion and calcium signaling pathway as expected.

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Identification of Differentially Expressed Gene after Femoral Fracture via Microarray Profiling

International Journal of Genomics ◽

10.1155/2014/208751 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Donggen Zhong

Keyword(s):

Gene Expression ◽

Calcium Signaling ◽

Signaling Pathway ◽

Femoral Fracture ◽

Differentially Expressed Gene ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Protein Protein Interaction ◽

Calcium Signaling Pathway

We aimed to investigate differentially expressed genes (DEGs) in different stages after femoral fracture based on rat models, providing the basis for the treatment of sport-related fractures. Gene expression data GSE3298 was downloaded from Gene Expression Omnibus (GEO), including 16 chips. All femoral fracture samples were classified into earlier fracture stage and later fracture stage. Total 87 DEGs simultaneously occurred in two stages, of which 4 genes showed opposite expression tendency. Out of the 4 genes,RestandCst8were hub nodes in protein-protein interaction (PPI) network. The GO (Gene Ontology) function enrichment analysis verified that nutrition supply related genes were enriched in the earlier stage and neuron growth related genes were enriched in the later stage. Calcium signaling pathway was the most significant pathway in earlier stage; in later stage, DEGs were enriched into 2 neurodevelopment-related pathways. Analysis of Pearson's correlation coefficient showed that a total of 3,300 genes were significantly associated with fracture time, none of which was overlapped with identified DEGs. This study suggested thatRestandCst8might act as potential indicators for fracture healing. Calcium signaling pathway and neurodevelopment-related pathways might be deeply involved in bone healing after femoral fracture.

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Bioinformatics Analysis Reveals the Potential Diagnostic Biomarkers for Abdominal Aortic Aneurysm

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.656263 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xinsheng Xie ◽

En ci Wang ◽

Dandan Xu ◽

Xiaolong Shu ◽

Yu fei Zhao ◽

...

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Bioinformatics Analysis ◽

Inflammatory Responses ◽

Expression Profiles ◽

Enrichment Analysis ◽

Aortic Aneurysms ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Abdominal Aortic

Objectives: Abdominal aortic aneurysms (AAAs) are associated with high mortality rates. The genes and pathways linked with AAA remain poorly understood. This study aimed to identify key differentially expressed genes (DEGs) linked to the progression of AAA using bioinformatics analysis.Methods: Gene expression profiles of the GSE47472 and GSE57691 datasets were acquired from the Gene Expression Omnibus (GEO) database. These datasets were merged and normalized using the “sva” R package, and DEGs were identified using the limma package in R. The functions of these DEGs were assessed using Cytoscape software. We analyzed the DEGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein–protein interaction networks were assembled using Cytoscape, and crucial genes were identified using the Cytoscape plugin, molecular complex detection. Data from GSE15729 and GSE24342 were also extracted to verify our findings.Results: We found that 120 genes were differentially expressed in AAA. Genes associated with inflammatory responses and nuclear-transcribed mRNA catabolic process were clustered in two gene modules in AAA. The hub genes of the two modules were IL6, RPL21, and RPL7A. The expression levels of IL6 correlated positively with RPL7A and negatively with RPL21. The expression of RPL21 and RPL7A was downregulated, whereas that of IL6 was upregulated in AAA.Conclusions: The expression of RPL21 or RPL7A combined with IL6 has a diagnostic value for AAA. The novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of AAA.

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A competing endogenous RNA mechanism in glioblastoma is investigated by bioinformatics analysis

10.21203/rs.2.21101/v1 ◽

2020 ◽

Author(s):

Jinsheng Wang ◽

Yutao Wang ◽

Lei Gao ◽

Yuhua Zhao ◽

Junhua Liu ◽

...

Keyword(s):

Signaling Pathway ◽

Differentially Expressed Genes ◽

Lupus Erythematosus ◽

Bioinformatics Analysis ◽

Enrichment Analysis ◽

Dendritic Cell Maturation ◽

Vital Role ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

P53 Signaling

Abstract Background Glioblastoma (GBM) is the most aggressive and most lethal primary malignant brain tumor, the 5-year survival rate of which is less than 5%. Novel potential molecular and mechanism of GBM need to investigate.Materials and methods Microarray data of GSE15824 was downloaded from GEO. Differentially expressed genes and lncRNAs were screened by Limma package in R studio, and pathway enrichment analysis was performed by clusterprofiler package in R studio and IPA. The ceRNA mechanism was analyzed and predicted by several kinds of online public databases.ResultsThere were 567 differentially expressed genes and 121 differentially expressed lncRNAs in GBM. And differentially expressed genes were mainly enriched in Tuberculosis, Staphylococcus aureus infection, Systemic lupus erythematosus, Basal cell carcinoma, TGF-beta signaling pathway and p53 signaling pathway. Besides, Neuroinflammation signaling pathway, Role of NFAT in regulation of the immune response, and Dendritic cell maturation were significantly activated in GBM. According to the analysis of target miRNAs of SEM4D and OSER1-AS1, a possible ceRNA mechanism OSER1-AS1/hsa-miR-520h/SEMA4D axis was predicted in GBM.Conclusion Bioinformatics analysis was employed to analyze GSE15824 chip, and predict the potential mechanism. The results revealed that the ceRNA mechanism, OSER1-AS1/hsa-miR-520h/SEMA4D axis, might play a vital role in GBM.

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Involvement of the miR-363-5p/P2RX4 Axis in Regulating Schwann Cell Phenotype after Nerve Injury

International Journal of Molecular Sciences ◽

10.3390/ijms222111601 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11601

Author(s):

Eun-Jung Sohn ◽

Yun-Kyeong Nam ◽

Hwan-Tae Park

Keyword(s):

Calcium Signaling ◽

Signaling Pathway ◽

Schwann Cells ◽

Nerve Injury ◽

Target Genes ◽

Adenosine Monophosphate ◽

Cell Phenotype ◽

Pathway Enrichment Analysis ◽

Guanine Nucleotide Binding Protein ◽

Calcium Signaling Pathway

Although microRNAs (miRNAs or miRs) have been studied in the peripheral nervous system, their function in Schwann cells remains elusive. In this study, we performed a microRNA array analysis of cyclic adenosine monophosphate (cAMP)-induced differentiated primary Schwann cells. KEGG pathway enrichment analysis of the target genes showed that upregulated miRNAs (mR212-5p, miR335, miR20b-5p, miR146b-3p, and miR363-5p) were related to the calcium signaling pathway, regulation of actin cytoskeleton, retrograde endocannabinoid signaling, and central carbon metabolism in cancer. Several key factors, such as purinergic receptors (P2X), guanine nucleotide-binding protein G(olf) subunit alpha (GNAL), P2RX5, P2RX3, platelet-derived growth factor receptor alpha (PDGFRA), and inositol 1,4,5-trisphosphate receptor type 2 (ITPR2; calcium signaling pathway) are potential targets of miRNAs regulating cAMP. Our analysis revealed that miRNAs were differentially expressed in cAMP-treated Schwann cells; miRNA363-5p was upregulated and directly targeted the P2X purinoceptor 4 (P2RX4)-UTR, reducing the luciferase activity of P2RX4. The expression of miRNA363-5p was inhibited and the expression of P2RX4 was upregulated in sciatic nerve injury. In contrast, miRNA363-5p expression was upregulated and P2RX4 expression was downregulated during postnatal development. Of note, a P2RX4 antagonist counteracted myelin degradation after nerve injury and increased pERK and c-Jun expression. Interestingly, a P2RX4 antagonist increased the levels of miRNA363-5p. This study suggests that a double-negative feedback loop between miRNA363-5p and P2RX4 contributes to the dedifferentiation and migration of Schwann cells after nerve injury.

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MicroRNA-140-5p inhibits cell proliferation, migration and promotes cell apoptosis in gastric cancer through the negative regulation of THY1-mediated Notch signaling

Bioscience Reports ◽

10.1042/bsr20181434 ◽

2019 ◽

Vol 39 (7) ◽

Cited By ~ 7

Author(s):

Kun Wu ◽

Jun Zou ◽

Chao Lin ◽

Zhi-Gang Jie

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Notch Signaling ◽

Signaling Pathway ◽

Expression Profiles ◽

Differentially Expressed Gene ◽

Notch Signaling Pathway ◽

Differentially Expressed ◽

Migration And Invasion ◽

Enhanced Expression

Abstract Studies have highlighted the importance of microRNAs (miRs) in the development of various cancers, including gastric cancer (GC), a commonly occurring malignancy, accompanied by high recurrence and metastasis rate. The aim of the current study was to investigate the role of miR-140-5p in GC. Microarray expression profiles were initially employed to screen the differentially expressed gene related to GC, and the miR regulating the gene was predicted accordingly. The data obtained indicated that thymus cell antigen 1 (THY1) was differentially expressed in GC and confirmed to be a target gene of miR-140-5p. Poorly expressed miR-140-5p and highly expressed THY1 were observed in the GC tissues. SGC-7901 cells were treated with miR-140-5p mimic/inhibitor, siRNA against THY1 and siRNA against Notch1 in order to determine their regulatory roles in GC cell activities. The relationship of miR-140-5p, THY1 and the Notch signaling pathway was subsequently identified. Moreover, cell proliferation, migration, invasion and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), wound-healing, transwell assay and flow cytometry, respectively. The overexpression of miR-140-5p and silencing of THY1 resulted in a diminished expression of the Notch signaling pathway-related proteins, as well as inhibited proliferation, migration and invasion of GC cells, enhanced expression of pro-apoptotic proteins in addition to elevated apoptosis rate. Taken together, the present study suggests that miR-140-5p directly targets and negatively regulates THY1 expression and inhibits activation of the Notch signaling pathway, whereby the up-regulation of miR-140-5p inhibits development of GC, highlighting the promise of miR-140-5p as a potential target for GC treatment.

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Microarray analysis of gene expression in mouse aorta reveals role of the calcium signaling pathway in control of atherosclerosis susceptibility

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01095.2008 ◽

2009 ◽

Vol 296 (5) ◽

pp. H1336-H1343 ◽

Cited By ~ 20

Author(s):

Zuobiao Yuan ◽

Toru Miyoshi ◽

Yongde Bao ◽

Jason P. Sheehan ◽

Alan H. Matsumoto ◽

...

Keyword(s):

Gene Expression ◽

Calcium Signaling ◽

Signaling Pathway ◽

Oxidized Ldl ◽

Atherosclerotic Lesion ◽

Differentially Expressed ◽

Monocyte Chemoattractant Protein 1 ◽

Monocyte Chemoattractant ◽

Monocyte Chemoattractant Protein ◽

Calcium Signaling Pathway

Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit a marked difference in atherosclerotic lesion formation when deficient in apolipoprotein E (apoE−/−), and the arterial wall has been identified as a source of the difference in atherosclerosis susceptibility. In the present study, differences in gene expression in aortic walls of the two strains were analyzed by microarrays. Total RNA was extracted from the aorta of 6-wk-old female B6 and C3H apoE−/− mice fed a chow or Western diet. There were 1,514 genes in chow fed mice and 590 genes in Western fed mice that were found to be differentially expressed between the two strains. Pathway analysis of differentially expressed genes suggested a role for the calcium signaling pathway in regulating atherosclerosis susceptibility. Oxidized LDL (oxLDL) induced a dose-dependent rise in cytosolic calcium levels in B6 endothelial cells. oxLDL-induced monocyte chemoattractant protein-1 production was inhibited by pretreatment with calcium chelator EGTA or intracellular calcium trapping compound BAPTA, indicating that calcium ions mediate the effect of oxLDL on monocyte chemoattractant protein-1 induction. The present findings demonstrate involvement of the calcium signaling pathway in the inflammatory process of atherogenesis.

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Identification of Differentially Expressed Genes and Signaling Pathways Related to Ovarian Endometriosis by Integrated Bioinformatics Analysis

10.21203/rs.3.rs-80648/v1 ◽

2020 ◽

Author(s):

Kainan Lin ◽

Zhenyan Pan ◽

Renke He ◽

Hanchu Wang ◽

Kai Zhou ◽

...

Keyword(s):

Mrna Expression ◽

Signaling Pathway ◽

Differentially Expressed Genes ◽

Kegg Pathway ◽

Expression Profiles ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Go Analysis ◽

Pathway Enrichment

Abstract Purpose: Endometriosis was a common gynecological disease, however, the specific mechanism and the key molecules of endometriosis remained uncertain. This study aimed to single out key genes associated with poor prognosis, and further uncover underlying mechanisms.Methods: Data regarding mRNA expression profiles used in this study were retrieved from the Gene Expression Omnibus (GEO) database, a total of three mRNA expression profiles were included for subsequent analysis (GSE31515, GSE58178 and GSE120103). Then, we conducted Gene Ontology analysis (GO analysis), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis by the software R.Results: A total of 304 differentially expressed genes (DEGs) between endometriosis tissues and normal endometrium tissues were identified in integrated analysis, including 185 up-regulated genes and 119 down-regulated genes. GO analysis reveals that the DEGs of endometriosis were closely associated with molecular origin of bacteria. KEGG pathway enrichment analysis indicates that the DEGs were mainly involved in AGE-RAGE signaling pathway in diabetic complications. In addition, PPI of these DEGs was visualized by Cytoscape platform with utilization of Search Tool for the Retrieval of Interacting Genes (STRING). PPI analysis identifies 10 potential DEGs-related protein targets, including CCND1, IL6, CCL2, COL1A2, PTGS2, VCAM1, COL3A1, ELN, SERPINE1, HSP90B1. Conclusion: In conclusion, the present study reveals that bacterial contamination, defect of female reproductive system development, retrograde menstruation and the AGE-RAGE signaling pathway may be involved in the development of endometriosis In addition, these identified DEGs may be of clinical significance for the diagnosis and treatment of the endometriosis.

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Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415007242 ◽

2015 ◽

Vol 7 (1) ◽

pp. 91-101 ◽

Cited By ~ 5

Author(s):

L. Chen ◽

J. Yue ◽

X. Han ◽

J. Li ◽

Y. Hu

Keyword(s):

Calcium Signaling ◽

Signaling Pathway ◽

Pathway Analysis ◽

Intrauterine Growth Restriction ◽

Kegg Pathway ◽

Growth Restriction ◽

Differentially Expressed ◽

Intrauterine Growth ◽

Kegg Pathway Analysis ◽

Calcium Signaling Pathway

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

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Calcium Signaling Alterations Caused by Epigenetic Mechanisms in Pancreatic Cancer: From Early Markers to Prognostic Impact

Cancers ◽

10.3390/cancers12071735 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1735 ◽

Cited By ~ 1

Author(s):

Cleandra Gregório ◽

Sheila Coelho Soares-Lima ◽

Bárbara Alemar ◽

Mariana Recamonde-Mendoza ◽

Diego Camuzi ◽

...

Keyword(s):

Dna Methylation ◽

Calcium Signaling ◽

Signaling Pathway ◽

Tumor Biology ◽

The Cancer Genome Atlas ◽

Ductal Adenocarcinoma ◽

Pathway Enrichment Analysis ◽

Prognostic Impact ◽

Phenotypic Effect ◽

Calcium Signaling Pathway

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high mortality rates. PDAC initiation and progression are promoted by genetic and epigenetic dysregulation. Here, we aimed to characterize the PDAC DNA methylome in search of novel altered pathways associated with tumor development. We examined the genome-wide DNA methylation profile of PDAC in an exploratory cohort including the comparative analyses of tumoral and non-tumoral pancreatic tissues (PT). Pathway enrichment analysis was used to choose differentially methylated (DM) CpGs with potential biological relevance. Additional samples were used in a validation cohort. DNA methylation impact on gene expression and its association with overall survival (OS) was investigated from PDAC TCGA (The Cancer Genome Atlas) data. Pathway analysis revealed DM genes in the calcium signaling pathway that is linked to the key pathways in pancreatic carcinogenesis. DNA methylation was frequently correlated with expression, and a subgroup of calcium signaling genes was associated with OS, reinforcing its probable phenotypic effect. Cluster analysis of PT samples revealed that some of the methylation alterations observed in the Calcium signaling pathway seemed to occur early in the carcinogenesis process, a finding that may open new insights about PDAC tumor biology.

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