scholarly journals Identification of differentially expressed genes and signalling pathways related to ovarian endometriosis based on integrated bioinformatic analysis

2021 ◽  
Author(s):  
Kainan Lin ◽  
Zhenyan Pan ◽  
Renke He ◽  
Hanchu Wang ◽  
Kai Zhou ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Protein Processing ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Channel Activity ◽  
Voltage Gated ◽  
Pathway Enrichment

Abstract Purpose Endometriosis is a common gynaecological disease; however, the specific mechanism and the key molecules involved in endometriosis have not been elucidated. This study aimed to identify 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, and a total of three mRNA expression profiles were included in subsequent analyses (GSE31515, GSE58178 and GSE120103). We divided all differentially expressed genes (DEGs) into up-regulated and down-regulated groups. Then, we conducted Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis using R software.Results A total of 304 DEGs were identified between endometriosis tissues and normal endometrium tissues using integrated analysis, including 185 up-regulated genes and 119 down-regulated genes. GO analysis revealed that the up-regulated DEGs of endometriosis were closely associated with voltage-gated calcium channel activity, whereas the down-regulated DEGs were enriched in uterus development. KEGG pathway enrichment analysis indicated that the up-regulated DEGs were mainly involved in cytokine-cytokine receptor interaction, whereas down-regulated DEGs were enriched in protein processing in the endoplasmic reticulum. In addition, PPIs of these DEGs were visualized using the Cytoscape platform and the Search Tool for the Retrieval of Interacting Genes (STRING). PPI analysis identified 10 potential DEG-related protein targets, including CCND1, IL6, CCL2, COL1A2, PTGS2, VCAM1, COL3A1, ELN, SERPINE1, and HSP90B1. Conclusion In conclusion, the present study reveals that voltage-gated calcium channel activity, uterus development, cytokine-cytokine receptor interaction and protein processing in the endoplasmic reticulum may be involved in the development of endometriosis. In addition, these identified DEGs may exhibit clinical significance for the diagnosis and treatment of endometriosis.

scholarly journals Identification of Differentially Expressed Genes and Signalling Pathways Related to Ovarian Endometriosis Based on Integrated Bioinformatic Analysis

2021 ◽  
Author(s):  
Kainan Lin ◽  
Zhenyan Pan ◽  
Renke He ◽  
Hanchu Wang ◽  
Kai Zhou ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Protein Processing ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Channel Activity ◽  
Voltage Gated ◽  
Pathway Enrichment

Abstract Purpose: Endometriosis is a common gynaecological disease; however, the specific mechanism and the key molecules involved in endometriosis have not been elucidated. This study aimed to identify 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, and a total of three mRNA expression profiles were included in subsequent analyses (GSE31515, GSE58178 and GSE120103). We divided all differentially expressed genes (DEGs) into up-regulated and down-regulated groups. Then, we conducted Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis using R software.Results: A total of 304 DEGs were identified between endometriosis tissues and normal endometrium tissues using integrated analysis, including 185 up-regulated genes and 119 down-regulated genes. GO analysis revealed that the up-regulated DEGs of endometriosis were closely associated with voltage-gated calcium channel activity, whereas the down-regulated DEGs were enriched in uterus development. KEGG pathway enrichment analysis indicated that the up-regulated DEGs were mainly involved in cytokine-cytokine receptor interaction, whereas down-regulated DEGs were enriched in protein processing in the endoplasmic reticulum. In addition, PPIs of these DEGs were visualized using the Cytoscape platform and the Search Tool for the Retrieval of Interacting Genes (STRING). PPI analysis identified 10 potential DEG-related protein targets, including CCND1, IL6, CCL2, COL1A2, PTGS2, VCAM1, COL3A1, ELN, SERPINE1, and HSP90B1. Conclusion: In conclusion, the present study reveals that voltage-gated calcium channel activity, uterus development, cytokine-cytokine receptor interaction and protein processing in the endoplasmic reticulum may be involved in the development of endometriosis. In addition, these identified DEGs may exhibit clinical significance for the diagnosis and treatment of endometriosis.

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

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.

scholarly journals Identification of Potential Genetic Biomarkers and Target Genes of Peri-Implantitis Using Bioinformatics Tools

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Xiaogen Zhang ◽  
Zhifa Wang ◽  
Li Hu ◽  
Xiaoqing Shen ◽  
Chundong Liu
Keyword(s):  
Target Genes ◽  
Kegg Pathway ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Venn Diagram ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Potential Target ◽  
Genetic Biomarkers

Objectives. To investigate potential genetic biomarkers of peri-implantitis and target genes for the therapy of peri-implantitis by bioinformatics analysis of publicly available data. Methods. The GSE33774 microarray dataset was downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) between peri-implantitis and healthy gingival tissues were identified using the GEO2R tool. GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database and the Metascape tool, and the results were expressed as a bubble diagram. The protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized using Cytoscape. The hub genes were screened by the cytoHubba plugin of Cytoscape. The potential target genes associated with peri-implantitis were obtained from the DisGeNET database and the Open Targets Platform. The intersecting genes were identified using the Venn diagram web tool. Results. Between the peri-implantitis group and the healthy group, 205 DEGs were investigated including 140 upregulated genes and 65 downregulated genes. These DEGs were mainly enriched in functions such as the immune response, inflammatory response, cell adhesion, receptor activity, and protease binding. The results of KEGG pathway enrichment analysis revealed that DEGs were mainly involved in the cytokine-cytokine receptor interaction, pathways in cancer, and the PI3K-Akt signaling pathway. The intersecting genes, including IL6, TLR4, FN1, IL1β, CXCL8, MMP9, and SPP1, were revealed as potential genetic biomarkers and target genes of peri-implantitis. Conclusions. This study provides supportive evidence that IL6, TLR4, FN1, IL1β, CXCL8, MMP9, and SPP1 might be used as potential target biomarkers for peri-implantitis which may provide further therapeutic potentials for peri-implantitis.

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

scholarly journals Is There a Relationship Between Psoriasis and Hepatitis C?: a Meta-analysis and Bioinformatics Investigation

2021 ◽  
Author(s):  
Yong Liu ◽  
Sheng Nan Cui ◽  
Meng Yao Duan ◽  
Zhi Li Dou ◽  
Yi Zhen Li ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Case Control ◽  
Cochrane Library ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Overlapping Genes ◽  
Cross Sectional ◽  
Pathway Enrichment

Abstract Background: The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection.Methods: We conducted a systematic review of the case-control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein-protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis. Results: We included 11 publications that reported a total of 11 studies (8 cross-sectional and 3 case-control). The case–control and cross-sectional studies included 25,047 psoriasis patients and 4,091,631 controls in total. Psoriasis was associated with a significant increase of prevalent hepatitis C (OR 1.72; 95% confidence interval [CI] (1.17-2.52)). A total of 389 significant genes were common to both hepatitis C and psoriasis, which mainly involved IL6, TNF, IL10, ALB, STAT3 and CXCL8. The module and pathway enrichment analyses showed that the common genes had the potential to influence varieties of biological pathways, including the inflammatory response, cytokine activity, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, which play an important role in the pathogenesis of hepatitis C and psoriasis.Conclusion: Patients with psoriasis display increased prevalence of hepatitis C and the basic related mechanisms between hepatitis C and psoriasis had been preliminarily clarified.

scholarly journals Identification of Differentially Expressed Genes and associated pathways common to Eyelid and Non-Ocular Basal Cell Carcinoma to understand the Molecular Biology of BCC

2021 ◽  
Author(s):  
Perumal Jayaraj ◽  
Seema Sen ◽  
Pranjal Vats ◽  
Shefali Dahiya ◽  
Vanshika Mohindroo
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Malignant Neoplasms ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Pathway Enrichment

Background: Eyelid BCC accounts for more than 90% of Eyelid malignant neoplasms. Various aberrant signalling pathways and genes in Non-Ocular BCC have been found whereas Eyelid bcc remains elusive. Objective: This study aims to find the common DEGs of Eyelid and Non-Ocular BCC using bioinformatic analysis and text mining to gain more insights into the molecular aspects common to both BCC non-ocular and Eyelid BCC and to identify common potential prognostic markers. Material and method: The Gene Expression profiles of Eyelid BCC (GSE103439) and Non-Ocular BCC (GSE53462) were obtained from the NCBI GEO database followed by identification of common DEGs. Protein-Protein interaction and Pathway Enrichment analysis of these screened genes was done using bioinformatic tools like STRING, Cytoscape and BiNGO, DAVID, KEGG respectively. Results: A total of 181 genes were found common in both datasets. A PPI network was formed for the screened genes and 20 HUB genes were sorted which included CTNNB1, MAPK14, BTRC, EGFR, ADAM17. Pathway enrichment of HUB genes showed that they were dysregulated in carcinogenic and apoptotic pathways that seem to play a role in the progression of both the BCC. Conclusion: The result and findings of bioinformatic analysis highlighted the molecular pathways and genes enriched in both Eyelid BCC as well as Non- Ocular BCC. The identified pathways should be studied further to recognise common molecular events that would lead to the progression of BCC. This may provide a window to explore the prognostic and therapeutic strategies common to both BCC. Keywords: Basal cell carcinoma (BCC), Cancer, Microarray, Ophthalmology, Tumour marker

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

2020 ◽  
Author(s):  
Zhiqiang Liu ◽  
Bolong Wang
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Kegg Pathway ◽  
Inflammatory Diseases ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Pharmacological Effects ◽  
Ppi Network ◽  
Pathway Enrichment ◽  
Pharmacological Mechanism

Abstract Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.

scholarly journals Transcriptomic analysis of Procambarus clarkii affected by “Black May” disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guoqing Shen ◽  
Xiao Zhang ◽  
Jie Gong ◽  
Yang Wang ◽  
Pengdan Huang ◽  
...  
Keyword(s):  
Procambarus Clarkii ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Apoptosis Pathway ◽  
Pathway Enrichment ◽  
Cellular Processes ◽  
Expression Of Genes ◽  
Muscle Tissues

AbstractEach year from April to May, high mortality rates are reported in red swamp crayfish (Procambarus clarkii) cultured in Jiangsu and other regions, in China, and this phenomenon has come to be known as “Black May” disease (BMD). Therefore, in order to investigate the possible causes of this disease, this study gathered BMD-affected P. clarkii samples and performed transcriptome analysis on hepatopancreas, gill, and muscle tissues. A total of 19,995,164, 149,212,804, and 222,053,848 clean reads were respectively obtained from the gills, muscle, and hepatopancreas of BMD-affected P. clarkii, and 114,024 unigenes were identified. The number of differentially expressed genes (DEGs) in gill, muscle, and hepatopancreas was 1703, 964, and 476, respectively. GO and KEGG enrichment analyses of the DEGs were then conducted. Based on KEGG pathway enrichment analysis, the most significantly differentially expressed pathways were mainly those involved with metabolism, human disease, and cellular processes. Further analysis of the significantly DEGs revealed that they were mainly related to the mitochondrial-mediated apoptosis pathway and that the expression of these DEGs was mostly down-regulated. Moreover, the expression of genes related to immune and metabolism-related pathways was also significantly down-regulated, and these significantly-inhibited pathways were the likely causes of P. clarkii death. Therefore, our results provide a basis for the identification of BMD causes.

scholarly journals Serum MiR-4687-3p Has Potential for Diagnosis and Carcinogenesis in Non-small Cell Lung Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Man Liu ◽  
Qiufang Si ◽  
Songyun Ouyang ◽  
Zhigang Zhou ◽  
Meng Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Validation Cohort ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Pathway Enrichment Analysis ◽  
Small Cell Lung ◽  
Invasion And Migration ◽  
Pathway Enrichment ◽  
And Migration

The lack of a useful biomarker partly contributes to the increased mortality of non-small cell lung cancer (NSCLC). MiRNAs have become increasingly appreciated in diagnosis of NSCLC. In the present study, we used microarray to screen 2,549 miRNAs in serum samples from the training cohort (NSCLC, n = 10; the healthy, n = 10) to discover differentially expressed miRNAs (DEMs). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was applied to validate the expression level of selected overexpressed DEMs of NSCLC in a validation cohort (NSCLC, n = 30; the healthy, n = 30). Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of the DEMs. The expression of the miRNAs in tissues was analyzed based on the TCGA database. Subsequently, the target genes of the miR-4687-3p were predicted by TargetScan. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were tested by R software (ClusterProfiler package). NSCLC cells were transfected with inhibitor or mimic to down-regulate or up-regulate the miR-4687-3p level. The function of miR-4687-3p on proliferation, invasion, and migration of lung cancer cells were investigated through CCK-8 and Transwell assays, respectively. In the results, we identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC = 0.679, 95%CI: 0.543–0.815) in the validation cohort. According to the TCGA database, we found that the miR-4687-3p level was significantly higher in NSCLC tissues than in normal lung tissues (p &lt; 0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-β signaling pathway were significantly enriched. Down-regulation of miR-4687-3p could suppress the proliferation, invasion, and migration of the NSCLC cells, compared with inhibitor negative control (NC). Meanwhile, overexpression of miR-4687-3p could promote the proliferation, invasion, and migration of the NSCLC cells compared with mimic NC. As a conclusion, our study first discovered that serum miR-4687-3p might have clinical potential as a non-invasive diagnostic biomarker for NSCLC and play an important role in the development of NSCLC.

scholarly journals Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

2017 ◽  
Vol 44 (2) ◽  
pp. 682-700 ◽  
Author(s):  
Lu Zhang ◽  
Lan-shan Huang ◽  
Gang Chen ◽  
Zhen-bo Feng
Keyword(s):  
Digestive Tract ◽  
Digestive System ◽  
Kegg Pathway ◽  
Univariate Analysis ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Clinical Value ◽  
Go Annotation ◽  
Pathway Enrichment ◽  
Target Mrnas

Background/Aims: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR-224-5p in cancers of the digestive tract is necessary. Methods: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224-5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. Conclusions: MiR-224-5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification.

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