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

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

International Journal of Endocrinology ◽

10.1155/2021/4926323 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Yinjie Gao ◽

Xiaosen Ma ◽

Huiping Wang ◽

Yunying Cui ◽

Yushi Zhang ◽

...

Keyword(s):

Calcium Signaling ◽

Signaling Pathway ◽

Quantitative Pcr ◽

Bioinformatics Analysis ◽

Expression Profiles ◽

Differentially Expressed Gene ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Mrna Levels ◽

Calcium Signaling Pathway

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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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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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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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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Main Pathways and Ion Channels Differentially Expressed in the Transcriptome of Male and Female Adult Angiostrongylus can-tonensis using a Deep Sequencing Approach

Iranian Journal of Parasitology ◽

10.18502/ijpa.v16i4.7874 ◽

2021 ◽

Author(s):

Yue Guo ◽

Hong Chang Zhou ◽

Hai Yan Dong ◽

Yun Liang Yao ◽

Bo Ying Xu ◽

...

Keyword(s):

Calcium Signaling ◽

Signaling Pathway ◽

Transforming Growth Factor ◽

Pentose Phosphate ◽

Differentially Expressed ◽

Receptor Interaction ◽

Female Adult ◽

Male And Female ◽

Sequencing Platform ◽

Calcium Signaling Pathway

Background: The adult stage is an important period in the life cycle of Angiostrongylus cantonensis, as it is at this stage that male and female worms produce thousands of fertilized eggs daily. Methods: To explore the transcriptional details of adult male and female A. cantonensis, three groups of male and female adult worms were collected, and their transcriptome profiles were analyzed using an Illumina next-generation sequencing platform. A total of 283,910,174 clean reads were obtained, and 137,626 unigenes and 237,059 transcripts were then generated. Unigenes were successfully annotated by querying the Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), NCBI non-redundant protein sequences (NR), PFAM, STRING, and SWISS-PROT databases. Then, differentially expressed genes (DEGs) between the 2 genders were identified. The GO and KEGG databases were used for DEG annotation, and a number of DEG annotations were enriched. Results: The results obtained from querying DEGs using the GO and KEGG databases revealed that male and female adult worms exhibited differences in metabolism and production. Protein phosphorylation, ion transport, and calcium transport were all significantly enriched according to GO annotation. A number of other pathways were also enriched according to KEGG enrichment annotation, including the pentose phosphate pathway, nitrogen metabolism, oocyte meiosis pathway, neuroactive ligand-receptor interaction, calcium signaling pathway, transforming growth factor β (TGF-β) signaling pathway etc. Conclusion: We hypothesized that the nervous system of the worm plays a key role in the physiological regulation of adult A. cantonensis, and based on this, the function of the calcium-signaling pathway should be investigated.

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Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2018/1431396 ◽

2018 ◽

Vol 2018 ◽

pp. 1-16 ◽

Cited By ~ 10

Author(s):

Shui Liu ◽

Xiaoxiao Yao ◽

Dan Zhang ◽

Jiyao Sheng ◽

Xin Wen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Gene Network ◽

Bioinformatics Analysis ◽

Expression Profiles ◽

Mrna Levels ◽

Qrt Pcr ◽

P53 Signaling ◽

Tf Gene ◽

P53 Signaling Pathway

Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver cancer, which has become the second most common cause of cancer-related mortality worldwide. To investigate the potential mechanisms of invasion and progression of HCC, bioinformatics analysis and validation by qRT-PCR were performed. We found 237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which were three cancer-related transcription factors. Subsequently, we constructed TF-gene network and miRNA-TF-mRNA network based on data obtained from mRNA and miRNA expression profiles for analysis of HCC. We found that 42 key genes from the TF-gene network including EGR1, FOS, and FOSB were most enriched in the p53 signaling pathway. The qRT-PCR data confirmed that mRNA levels of EGR1, FOS, and FOSB all were decreased in HCC tissues. In addition, we confirmed that the mRNA levels of CCNB1, CCNB2, and CHEK1, three key markers of the p53 signaling pathway, were all increased in HCC tissues by bioinformatics analysis and qRT-PCR validation. Therefore, we speculated that miR-181a-5p, which was upregulated in HCC tissues, could regulate FOS and EGR1 to promote the invasion and progression of HCC by p53 signaling pathway. Overall, the study provides support for the possible mechanisms of progression in HCC.

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Rutin restrains the growth and metastasis of mouse breast cancer cells by regulating the microRNA‐129‐1‐3p‐mediated calcium signaling pathway

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22794 ◽

2021 ◽

Author(s):

Qi Li ◽

Dongsheng Xu ◽

Zehui Gu ◽

Tengteng Li ◽

Peng Huang ◽

...

Keyword(s):

Breast Cancer ◽

Calcium Signaling ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Calcium Signaling Pathway ◽

Mouse Breast Cancer

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Identification of differentially expressed microRNAs in outgrowth embryos compared with blastocysts and non-outgrowth embryos in mice

Reproduction Fertility and Development ◽

10.1071/rd18161 ◽

2019 ◽

Vol 31 (4) ◽

pp. 645 ◽

Cited By ~ 6

Author(s):

Jihyun Kim ◽

Jaewang Lee ◽

Jin Hyun Jun

Keyword(s):

Bioinformatics Analysis ◽

Preimplantation Embryo ◽

Expression Profiles ◽

In Silico Analysis ◽

Differentially Expressed ◽

Recurrent Implantation Failure ◽

Preimplantation Embryo Development ◽

Mirna Expression Profiles ◽

Differentially Expressed Mirnas ◽

Silico Analysis

Recurrent implantation failure (RIF) is one of the main causes for the repeated failure of IVF, and the major reason for RIF is thought to be a miscommunication between the embryo and uterus. However, the exact mechanism underlying embryo–uterus cross-talk is not fully understood. The aim of the present study was to identify differentially expressed microRNAs (miRNAs) among blastocysts, non-outgrowth and outgrowth embryos in mice using microarray analysis. A bioinformatics analysis was performed to predict the potential mechanisms of implantation. The miRNA expression profiles differed significantly between non-outgrowth and outgrowth embryos. In all, 3163 miRNAs were detected in blastocysts and outgrowth embryos. Of these, 10 miRNA candidates (let-7b, miR-23a, miR-27a, miR-92a, miR-183, miR-200c, miR-291a, miR-425, miR-429 and miR-652) were identified as significant differentially expressed miRNAs of outgrowth embryos by in silico analysis. The expression of the miRNA candidates was markedly changed during preimplantation embryo development. In particular, let-7b-5p, miR-200c-3p and miR-23a-3p were significantly upregulated in outgrowth embryos compared with non-outgrowth blastocysts. Overall, differentially expressed miRNAs in outgrowth embryos compared with blastocysts and non-outgrowth embryos could be involved in embryo attachment, and interaction between the embryo proper and maternal endometrium during the implantation process.

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