Identification of novel miRNA-mRNA regulatory networks in contact dermatitis by integrated microarray analysis.
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ABSTRACT:
SUBMITTER: Werner P
PROVIDER: S-EPMC8246963 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nowadays, the current bioinformatic methods have been increasingly applied in the field of oncological research. In this study, we expect a better understanding of the molecular mechanism of gastric cancer from the bioinformatic methods. By systematically addressing the differential expression of microRNAs (miRNAs) and mRNAs between gastric cancer specimens and normal gastric specimens with the application of bioinformatics tools, A total of 206 DEGs and 38 DEMs were identified. The Gene Ontology (GO) analysis of Annotation, Visualization and Integrated Discovery (DAVID) database revealed that the differentially expressed genes (DEGs) were significantly enriched in biological process, molecular function and cellular component, while Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed DEGs were significantly enriched in 8 signal pathways. The miRNA-gene regulatory network was constructed based on 385 miRNA-gene (DEM-DEG) pairs, consisting of 35 miRNAs and 107 target genes. In the regulatory network, the top 5 up-regulated genes were Transmembrane Protease, Serine 11B (TMPRSS11B), regulator of G protein signaling 1 (RGS1), cysteine rich angiogenic inducer 61 (CYR61), inhibin subunit beta A (INHBA), syntrophin gamma 1 (SNTG1), and the top 5 down-regulated genes were tumor necrosis factor receptor superfamily, member 19 (TNFRSF19), pleckstrin homology domain containing B2 (PLEKHB2), Tax1 binding protein 3 (TAX1BP3), presenilin enhancer, gamma-secretase subunit (PSENEN), NME/NM23 nucleoside diphosphate kinase 3 (NME3). Based on the gastric cancer patient database from Kaplan-Meier Plotter tools, we found that 8 of 10 genes with most significant changes in the miRNA-gene regulatory network possessed a prognostic value for survival time of gastric cancer patients. Patients with higher level of RGS1, PLEKHB2, TAX1BP3 and PSENEN in gastric cancer had a longer survival time compared with the patients with lower level of these genes. On the contrary, patients with higher level of INHBA, SNTG1, TNFRSF19 and NME3 were found associated with a shorter survival time. In conclusion, our findings provided several potential targets regarding gastric cancer, which may result in a new strategy to treat gastric cancer from a system rather than a single-gene perspective.
| S-EPMC7847513 | biostudies-literature
Project description:Osteoarthritis (OA) is a common orthopedic degenerative disease, leading to high disability in activities of daily living. There remains an urgent need to identify the underlying mechanisms and identify new therapeutic targets in OA diagnosis and treatment. Circular RNAs (circRNAs) play a role in the development of multiple diseases. Many studies have reported that circRNAs regulate microRNAs (miRNAs) through an endogenous competitive mechanism. However, it remains unclear if an interplay between circRNAs, miRNAs, and target genes plays a deeper regulatory role in OA. Four datasets were downloaded from the GEO database, and differentially expressed circRNAs (DECs), differentially expressed miRNAs (DEMs), and differentially expressed genes (DEGs) were identified. Functional annotation and pathway enrichment analysis of DEGs and DECs were carried out to determine the main associated mechanism in OA. A protein–protein network (PPI) was constructed to analyze the function of, and to screen out, hub DEGs in OA. Based on the artificial intelligence prediction of protein crystal structures of two hub DEGs, TOP2A and PLK1, digitoxin and oxytetracycline were found to have the strongest affinity, respectively, with molecular docking. Subsequently, overlapping DEMs and miRNAs targeted by DECs obtained target DEMs (DETMs). Intersection of DEGs and genes targeted by DEMs obtained target DEGs (DETGs). Thus, a circRNA–miRNA–mRNA regulatory network was constructed from 16 circRNAs, 32 miRNAs, and 97 mRNAs. Three hub DECs have the largest number of regulated miRNAs and were verified through in vitro experiments. In addition, the expression level of 16 DECs was validated by RT-PCR. In conclusion, we constructed a circRNA–miRNA–mRNA regulatory network in OA and three new hub DECs, hsa_circ_0027914, hsa_circ_0101125, and hsa_circ_0102564, were identified as novel biomarkers for OA.
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Project description:Uterine fibroids (UF) are the most common benign gynecologic tumors and lead to heavy menstrual bleeding, severe anemia, abdominal pain, and infertility, which seriously harm a women's health. Unfortunately, the regulatory mechanisms of UF have not been elucidated. Recent studies have demonstrated that miRNAs play a vital role in the development of uterine fibroids. As a high-throughput technology, microarray is utilized to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between UF and myometrium. We identified 373 candidate DEGs and the top 100 DEMs. Function enrichment analysis showed that candidate DEGs were mainly enriched in biological adhesion, locomotion and cell migration, and collagen-containing extracellular matrix. Subsequently, protein-protein interaction (PPI) networks are constructed to analyze the functional interaction between DEGs and screen hub DEGs. Subsequently, the expression levels of hub DEGs were validated by real-time PCR of clinical UF samples. The DGIdb database was used to select candidate drugs for hub DEGs. Molecular docking was applied to test the affinity between proteins and drugs. Furthermore, target genes for 100 candidate DEMs were predicted by miRwalk3.0. After overlapping with 373 candidate DEGs, 28 differentially expressed target genes (DEGTs) were obtained. A miRNA-mRNA network was constructed to investigate the interactions between miRNA and mRNA. Additionally, two miRNAs (hsa-miR-381-3p and hsa-miR-181b-5p) were identified as hub DEMs and validated through RT-PCR. In order to better elucidate the pathogenesis of UF and the synergistic effect between miRNA and transcription factor (TF), we constructed a miRNA-TF-mRNA regulatory network. Meanwhile, in vitro results suggested that dysregulated hub DEMs were associated with the proliferation, migration, and apoptosis of UF cells. Our findings provided a novel horizon to reveal the internal mechanism and novel targets for the diagnosis and treatment of UF.
| S-EPMC8981149 | biostudies-literature
Project description:Early‑onset preeclampsia (EOPE) is a serious threat to maternal and foetal health. The present study aimed to identify potential biomarkers and targets for the treatment of EOPE. Expression profiles of placenta from patients with EOPE and healthy controls (GSE103542, GSE74341 and GSE44711) were downloaded from the Gene Expression Omnibus database. Integrated analysis revealed 246 genes and 28 microRNAs (miRNAs) that were differentially expressed between patients with EOPE and healthy controls. Differentially expressed genes (DEGs) were primarily enriched in 'biological processes', such as 'cell adhesion', 'female pregnancy', 'extracellular matrix organization' and 'response to hypoxia'. Significant pathways associated with DEGs primarily included 'focal adhesion', 'ECM‑receptor interaction', 'PI3K‑Akt signaling' and 'ovarian steroidogenesis'. A Protein‑Protein Interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database, and epidermal growth factor receptor, collagen α‑1(I) chain, secreted phosphoprotein 1, leptin (LEP), collagen α‑2(I) chain (COL1A2), plasminogen activator inhibitor 1 (SERPINE1), Thy‑1 membrane glycoprotein, bone morphogenetic protein 4, vascular cell adhesion protein 1 and matrix metallopeptidase 1 were identified as hub genes. The alterations of hsa‑miR‑937, hsa‑miR‑148b*, hsa‑miR‑3907, hsa‑miR‑367*, COL1A2, LEP and SERPINE1 in placenta were validated using our local samples. Our research showed that the expression of hsa‑miR‑937, hsa‑miR‑1486*, hsa‑miR‑3907, hsa‑miR‑367* and hub genes in the placenta were closely associated with the pathophysiology of EOPE. hsa‑miR‑937, hsa‑miR‑1486*, hsa‑miR‑3907, hsa‑miR‑367* and hub genes could serve as biomarkers for diagnosis and as potential targets for the treatment of EOPE.
| S-EPMC7646902 | biostudies-literature
Project description:The aim of the present study was to explore the miRNA-Gene regulatory mechanism in chronic lymphocytic leukemia (CLL), and identify new targets for the therapy of CLL. The miRNA expression dataset GSE62137 and mRNA expression dataset GSE22529 were downloaded from National Center of Biotechnology Information Gene Expression Omnibus database. In CLL samples compared with normal B cell samples, differentially expressed miRNAs (DEMs) were identified via the GEO2R instrument of GEO and differentially expressed genes (DEGs) were obtained via the limma package of R. Functional enrichment analysis of the DEGs was performed via the Database for Annotation, Visualization and Integrated Discovery. The targets of the DEMs were identified based on the miRNAWalk platform. The overlaps between the DEGs and the targets of the DEMs were selected, and the miRNA-Gene regulatory network was constructed based on the overlaps and the corresponding DEMs. A total of 63 DEMs and 504 DEGs were identified in CLL samples compared with normal B cell samples. Eleven enriched functional clusters of the DEGs were obtained. 405 miRNA-Gene regulatory pairs were identified. The miRNA-Gene regulatory pairs contained 351 target genes of the DEMs, including 9 overlaps with the DEGs. A miRNA-Gene regulatory network was constructed. Bioinformatics methods could help us develop a better understanding of the molecular mechanism of CLL. MiRNAs may play a critical role in regulating the process of CLL. They may affect CLL by regulating the processes of immunoreactivity and protein degradation. Genes such as Neurogenic Locus Notch Homolog Protein 2, PR/SET domain 4 and A-kinase anchoring protein 12 may be their regulating targets in CLL.
| S-EPMC5738675 | biostudies-literature
Project description:Parkinson's disease (PD) is the second-most common neurodegenerative disease, and its pathophysiology is associated with alpha-synuclein accumulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. MicroRNAs are small non-coding RNAs that regulate gene expression, and many previous studies have described their dysregulation in plasma, CSF, and in the brain of patients with PD. In this study, we aimed to provide a regulatory network analysis on differentially expressed miRNAs in the brain of patients with PD. Based on our systematic review with a focus on the substantia nigra and the putamen, we found 99 differentially expressed miRNAs in brain samples from patients with PD, which regulate 135 target genes. Five genes associated with neuronal survival (BCL2, CCND1, FOXO3, MYC, and SIRT1) were modulated by dysregulated miRNAs found in the substantia nigra and the putamen of patients with PD. The functional enrichment analysis found FoxO and PI3K-AKT signaling as pathways related to PD. In conclusion, our comprehensive analysis of brain-related miRNA-mRNA regulatory networks in PD showed that mechanisms involving neuronal survival signaling, such as cell cycle control and regulation of autophagy/apoptosis, may be crucial for the neurodegeneration of PD, being a promising way for novel disease-modifying therapies.
| S-EPMC8228551 | biostudies-literature
Project description:IntroductionDiabetic retinopathy (DR) is a major complication of diabetes and a leading cause of visual loss. This study aimed to explore biomarkers for DR that may provide additional reference to DR pathogenesis and development.MethodsThe differentially expressed genes (DEGs) between the DR and control samples in the GSE53257 dataset were identified. Logistics analyses were performed to identify DR-associated miRNAs and genes, and correlation analysis was performed to determine the correlation between them in GSE160306.ResultsA total of 114 DEGs in DR were identified in GSE53257. Three genes, including ATP5A1 (down), DAUFV2 (down), and OXA1L (down), were differentially expressed between DR and control samples in GSE160306. Univariate logistics analysis identified that ATP5A1 (OR=0.007, p = 1.40E-02), NDUFV2 (OR = 0.003, p = 6.40E-03), and OXA1L (OR = 0.093, p = 3.08E-02) were DR-associated genes. ATP5A1 and OXA1L were regulated by multiple miRNAs, of which hsa-let- 7b-5p (OR = 26.071, p = 4.40E-03) and hsa-miR-31-5p (OR = 4.188, p = 5.09E-02) were related to DR. ATP5A1 and OXA1L were closely correlated with each other in DR.ConclusionThe hsa-miR-31-5p-ATP5A1 and hsa-let-7b-5p-OXA1L axes might play novel and important roles in the pathogenesis and development of DR.
| S-EPMC10661965 | biostudies-literature
Project description:The dynamic temporal regulatory effects of microRNA are not well known. We introduce a technique for integrating miRNA and mRNA time series microarray data with known disease pathology. The integrated analysis includes identifying both mRNA and miRNA that are signi cantly similar to the quantitative pathology. Potential regulatory miRNA/mRNA target pairs are identi ed through databases of both predicted and validated pairs. Finally, potential target pairs are ltered by examining the second derivatives of the fold changes over time. Our system was used on genome-wide microarray expression data of mouse lungs (n = 160) following aspiration of multi-walled carbon nanotubes. This system shows promise of readily identifying miRNA for further study as potential biomarker use.
| S-EPMC4433490 | biostudies-literature
Project description:BackgroundEvidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function of circRNAs in gastric cancer (GC) are still unknown. Here, we aimed to determine the regulatory mechanism of circRNAs in GC.MethodsExpression profiles of circRNAs were downloaded from four Gene Expression Omnibus (GEO) microarray datasets. Expression profiles of miRNAs and mRNAs were collected from The Cancer Genome Atlas (TCGA) database. We used the robust rank aggregation method to identify differentially expressed circRNAs (DEcircRNAs) and a ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Functional and pathway enrichment analyses were performed and interactions between proteins were predicted using Cytoscape. Aa subnetwork regulatory module was built using the MCODE plugin.ResultsA total of eight DEcircRNAs, 240 DEmiRNAs, and 4578 DEmRNAs were identified. The circRNA-miRNA-mRNA network was constructed based on seven circRNAs, 33 miRNAs, 69 mRNAs in GC. GO and KEGG pathway analysis indicated DEmRNAs might be associated with GC onset and progression. A PPI network was established and four hub genes (MCM4, KIF23, MCM8, and NCAPD2) were determined from the network. Then a circRNA-miRNA-hub gene subnetwork was constructed based on the four DEcircRNAs, three DEmiRNAs, and four DEmRNAs.ConclusionsOur findings provide a deeper understanding the circRNA-related competing endogenous RNA regulatory mechanism in GC pathogenesis.
| S-EPMC6636116 | biostudies-literature
Project description:IntroductionMajor depressive disorder (MDD) is a recurrent, devastating mental disorder, which affects >350 million people worldwide, and exerts substantial public health and financial costs to society. Thus, there is a significant need to discover innovative therapeutics to treat depression efficiently. Stress-induced dysfunction in the subtype of neuronal cells and the change of synaptic plasticity and structural plasticity of nucleus accumbens (NAc) are implicated in depression symptomology. However, the molecular and epigenetic mechanisms and stresses to the NAc pathological changes in depression remain elusive.Materials and methodsIn this study, treatment group mice were treated continually with the chronic unpredictable mild stress (CUMS) until expression of depression-like behaviors were found. Depression was confirmed with sucrose preference, novelty-suppressed feeding, forced swimming, and tail suspension tests. We applied high-throughput RNA sequencing to assess microRNA expression and transcriptional profiles in the NAc tissue from depression-like behaviors mice and control mice. The regulatory network of miRNAs/mRNAs was constructed based on the high-throughput RNA sequence and bioinformatics software predictions.ResultsA total of 17 miRNAs and 10 mRNAs were significantly upregulated in the NAc of CUMS-induced mice with depression-like behaviors, and 12 miRNAs and 29 mRNAs were downregulated. A series of bioinformatics analyses showed that these altered miRNAs predicted target mRNA and differentially expressed mRNAs were significantly enriched in the MAPK signaling pathway, GABAergic synapse, dopaminergic synapse, cytokine-cytokine receptor interaction, axon guidance, regulation of autophagy, and so on. Furthermore, dual luciferase report assay and qRT-PCR results validated the miRNA/mRNA regulatory network.ConclusionThe deteriorations of GABAergic synapses, dopaminergic synapses, neurotransmitter synthesis, as well as autophagy-associated apoptotic pathway are associated with the molecular pathological mechanism of CUMS-induced depression.
| S-EPMC6421879 | biostudies-literature