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.

Dendritic cells originating exosomal miR-193b-3p induces regulatory T cells to alleviate liver transplant rejection

“…Among the many components of exosomes, miRNAs represent essential messenger molecules [42] that could achieve post-transcriptional regulation. Approximately 70% of all miRNAs are expressed in the liver [43] . Accordingly, miRNAs serve as potential indicators of allograft function following LT. Freecirculating miRNAs (fc-miRNAs) are usually non-speci c and unstable as they bind to lipoproteins or proteins released from cells either during apoptosis or necrosis and exhibit similar changes in a variety of disease or pathological states [44] .…”

Epigenetics of alcohol-related liver diseases

“…Alcohol promotes inflammation, steatosis, and subsequently fibrosis by regulating multiple miRNAs. [84] , [85] , [86] , [87] , [88] , [89] , [90] , [91] In alcohol-fed murine models, miR-132 and miR-155 levels were upregulated in Kupffer cells. 92 MiR-155 enhances the proinflammatory effects of alcohol on Kupffer cells.…”