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Article

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

1
Institute of Bioinformatics, University Medicine Greifswald, Felix-Hausdorff-Str. 8, 17475 Greifswald, Germany
2
Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland
3
Department of General and Transplantation Surgery, County Hospital, 70-111 Szczecin, Poland
4
Center for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain
5
Liver Unit. Clinical Universidad de Navarra, 31008 Pamplona, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7368; https://doi.org/10.3390/ijms21197368
Received: 4 August 2020 / Revised: 18 September 2020 / Accepted: 2 October 2020 / Published: 6 October 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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. View Full-Text
Keywords: liver disease; microRNA; regulatory networks liver disease; microRNA; regulatory networks
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MDPI and ACS Style

Gholizadeh, M.; Szelag-Pieniek, S.; Post, M.; Kurzawski, M.; Prieto, J.; Argemi, J.; Drozdzik, M.; Kaderali, L. Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases. Int. J. Mol. Sci. 2020, 21, 7368. https://doi.org/10.3390/ijms21197368

AMA Style

Gholizadeh M, Szelag-Pieniek S, Post M, Kurzawski M, Prieto J, Argemi J, Drozdzik M, Kaderali L. Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases. International Journal of Molecular Sciences. 2020; 21(19):7368. https://doi.org/10.3390/ijms21197368

Chicago/Turabian Style

Gholizadeh, Maryam, Sylwia Szelag-Pieniek, Mariola Post, Mateusz Kurzawski, Jesus Prieto, Josepmaria Argemi, Marek Drozdzik, and Lars Kaderali. 2020. "Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases" International Journal of Molecular Sciences 21, no. 19: 7368. https://doi.org/10.3390/ijms21197368

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