Dataset Information

Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases.

ABSTRACT: Liver diseases are important causes of morbidity and mortality worldwide. The aim of this study was to identify differentially expressed microRNAs (miRNAs), target genes, and key pathways as innovative diagnostic biomarkers in liver patients with different pathology and functional state. We determined, using RT-qPCR, the expression of 472 miRNAs in 125 explanted livers from subjects with six different liver pathologies and from control livers. ANOVA was employed to obtain differentially expressed miRNAs (DEMs), and miRDB (MicroRNA target prediction database) was used to predict target genes. A miRNA-gene differential regulatory (MGDR) network was constructed for each condition. Key miRNAs were detected using topological analysis. Enrichment analysis for DEMs was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We identified important DEMs common and specific to the different patient groups and disease progression stages. hsa-miR-1275 was universally downregulated regardless the disease etiology and stage, while hsa-let-7a*, hsa-miR-195, hsa-miR-374, and hsa-miR-378 were deregulated. The most significantly enriched pathways of target genes controlled by these miRNAs comprise p53 tumor suppressor protein (TP53)-regulated metabolic genes, and those involved in regulation of methyl-CpG-binding protein 2 (MECP2) expression, phosphatase and tensin homolog (PTEN) messenger RNA (mRNA) translation and copper homeostasis. Our findings show a novel panel of deregulated miRNAs in the liver tissue from patients with different liver pathologies. These miRNAs hold potential as biomarkers for diagnosis and staging of liver diseases.

SUBMITTER: Gholizadeh M

PROVIDER: S-EPMC7582243 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases.

Gholizadeh Maryam M Szelag-Pieniek Sylwia S Post Mariola M Kurzawski Mateusz M Prieto Jesus J Argemi Josepmaria J Drozdzik Marek M Kaderali Lars L

International journal of molecular sciences 20201006 19

Liver diseases are important causes of morbidity and mortality worldwide. The aim of this study was to identify differentially expressed microRNAs (miRNAs), target genes, and key pathways as innovative diagnostic biomarkers in liver patients with different pathology and functional state. We determined, using RT-qPCR, the expression of 472 miRNAs in 125 explanted livers from subjects with six different liver pathologies and from control livers. ANOVA was employed to obtain differentially expresse ...[more]

PMID: 33036164

Similar Datasets

Project description:Background: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy. Large-scale genetics or epigenetics studies of NPC have been relatively scarce and sporadic, and there are no effective targeted drugs for NPC. Integrative analysis of multiple different omics profiles has been proved to be an effective approach to shed new light on cancer. Methods: We developed a pipeline to aggregate consensus differentially expressed genes (DEGs) from multiple expression datasets from different platforms. Integrated bioinformatics analysis of DNA methylation and gene expression was used to prioritize key genes in NPC. We explored the biological and clinical importance of key genes, combining differential co-expression analysis, network analysis of protein-protein and microRNA (miRNA)-target interactions, and pan-cancer survival analysis. Results: We obtained 668 upregulated and 594 downregulated consensus DEGs, which enriched in the PI3K-AKT, NF-κB and immune-related pathways. In NPC, 98% of 3364 differentially methylated sites were hypermethylated. Actively expressed EBV gene EBNA1 was positively correlated with over-expressed genes coding DNA methyltransferase and Polycomb group proteins, suggesting that EBV infection may have an important role in the hypermethylation of NPC. Through integrated analysis of DNA methylation and mRNA and miRNA expression profiles, we prioritized 56 hypermethylated downregulated genes, including 7 tumor suppressor genes, and constructed a miRNA-target regulation network consisting of 12 hypermethylated miRNAs and 25 upregulated oncogenes. The promoter hypermethylation of PRKCB causing its downregulation was validated by experimental results and higher PRKCB expression was associated with longer overall survival in head-neck squamous cell carcinoma, suggesting the potential of PRKCB as a promising disease biomarker for NPC. Conclusions: Our integrative analysis provides reliable key genes for candidate biomarkers for diagnosis and prognosis in NPC. Based on the combined evidence of promoter hypermethylation, expression up-regulation, and association with overall survival, genes such as SCUBE2, PRKCB, IKZF1, MAP4K1, and GATA6 could be promising novel diagnostic biomarkers, and miRNAs including MIR150, MIR152, and MIR34 could be candidate prognosis biomarkers.

Dataset Information

Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases.

Publications

Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets