Analysis of miRNAs Profiles in Serum of Patients With Steatosis and Steatohepatitis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common chronic liver diseases worldwide, affecting 25% of the world population. In recent years, there has been increasing evidence for the involvement of microRNAs in the epigenetic regulation of genes taking part in the development of steatosis and steatohepatitis—two main stages of NAFLD pathogenesis. In the present study, miRNA profiles were studied in groups of patients with steatosis and steatohepatitis to compare the characteristics of RNA-dependent epigenetic regulation of the stages of NAFLD development. According to the results of miRNA screening, 23 miRNAs were differentially expressed serum in a group of patients with steatohepatitis and 2 in a group of patients with steatosis. MiR-195-5p and miR-16-5p are common differentially expressed miRNAs for both steatosis and steatohepatitis. We analyzed the obtained results: the search for target genes for the differentially expressed miRNAs in our study and the subsequent gene set enrichment analysis performed on KEGG and REACTOME databases revealed which metabolic pathways undergo changes in RNA-dependent epigenetic regulation in steatosis and steatohepatitis. New findings within the framework of this study are the dysregulation of neurohumoral pathways in the pathogenesis of NAFLD as an object of changes in RNA-dependent epigenetic regulation. The miRNAs differentially expressed in our study were found to target 7% of genes in the classic pathogenesis of NAFLD in the group of patients with steatosis and 50% in the group of patients with steatohepatitis. The effects of these microRNAs on genes for the pathogenesis of NAFLD were analyzed in detail. MiR-374a-5p, miR-1-3p and miR-23a-3p do not target genes directly involved in the pathogenesis of NAFLD. The differentially expressed miRNAs found in this study target genes largely responsible for mitochondrial function. The role of miR-423-5p, miR-143-5p and miR-200c-3 in regulating apoptotic processes in the liver and hepatocarcinogenesis is of interest for future experimental studies. These miR-374a, miR-143, miR-1, miR-23a, and miR-423 have potential for steatohepatitis diagnosis and are poorly studied in the context of NAFLD. Thus, this work opens up prospects for further studies of microRNAs as diagnostic and therapeutic biomarkers for NAFLD.

Detangling the interrelations between MAFLD, insulin resistance, and key hormones

“…Finally, a serum microRNA (miRNA) profile revealed the potential relationship between different miRNAs and the presence of steatosis or steatohepatitis in 16 patients. It was reported that miR-374a-5p, miR-1-3p, and miR-23a-3p do not target genes that are directly involved in the pathogenesis of MAFLD [78]. On the other hand, the specific roles of some miRNAs are still unknown.…”

“…It has been considered a therapeutic target, given that its inhibition of the L/R-type pyruvate kinase (PKLR) could lead to a decrease in de novo lipogenesis (DNL) and oxidative phosphorylation in mitochondria, having a positive effect in the early stages of MAFLD. However, this particular miRNA was also found to inhibit the AMPK complex, thus contributing to progression to steatohepatitis as well as suppressing tumor necrosis factor (TNF) and Fas cell surface death receptor (FAS), possibly contributing to fibrosis and establishment of HCC [78].…”

Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death

“…miRNAs and long non-coding RNAs (lncRNAs) are highly confirmed to play a crucial role in mediating the progression of diseases, including NASH. An altered hepatic miRNA profile has been shown in NASH in both human and animal models [ 35 , 36 ] and more evidence demonstrated the role of miRNAs in liver functions [ 37 ]. Concerning lncRNAs, their role in inflammation-related diseases, especially NASH, was mentioned in detail in a recent review by Shabgah et al, [ 38 ] who presented multiple examples of NAFLD-related lncRNAs and their potential mechanisms contributing to disease progression.…”

Quantitative Prediction of Steatosis in Patients with Non-Alcoholic Fatty Liver by Means of Hepatic MicroRNAs Present in Serum and Correlating with Hepatic Fat

“…The relevance of some of the miRNAs selected after our regression modeling and biological fine-tuning was reinforced by previous studies searching for miRNA biomarkers. Thus, miR-23a-3p and miR-19a-3p were found to be deregulated (with an opposite trend) in the serum of patients with NASH [ 22 ]. Similarly, miR-19a and b were both upregulated in the serum of simple steatosis NAFLD patients [ 23 ], whereas in a different study, miR-30a-3p was also substantially upregulated in NAFLD patients, and its suppression attenuated hepatic steatosis in HepG2 cells [ 24 ].…”