MicroRNA-29c Acting on FOS Plays a Significant Role in Nonalcoholic Steatohepatitis Through the Interleukin-17 Signaling Pathway

Abstract

Nonalcoholic fatty liver disease is the most common hepatic disease in western countries and is even more ubiquitous in Asian countries. Our study determined that TH17/Treg cells were imbalanced in animal models. Based on our interest in the mechanism underlying TH17/Treg cell imbalance in nonalcoholic fatty liver mice, we conducted a joint bioinformatics analysis to further investigate this process. Common gene sequencing analysis was based on one trial from one sequencing platform, where gene expression analysis and enrichment analysis were the only analyses performed. We compared different sequencing results from different trials performed using different sequencing platforms, and we utilized the intersection of these analytical results to perform joint analysis. We used a bioinformatics analysis method to perform enrichment analysis and map interaction network analysis and predict potential microRNA sites. Animal experiments were also designed to validate the results of the data analysis based on quantitative polymerase chain reaction (qPCR) and western blotting. Our results revealed 8 coexisting differentially expressed genes (DEGs) and 7 hinge genes. The identified DEGs may influence nonalcoholic steatosis hepatitis through the interleukin-17 pathway. We found that microRNA-29c interacts with FOS and IGFBP1. Polymerase chain reaction analyses revealed both FOS and microRNA-29c expression in NASH mice, and western blot analyses indicated the same trend with regard to FOS protein levels. Based on these results, we suggest that microRNA-29c acts on FOS via the interleukin-17 signaling pathway to regulate TH17/Treg cells in NASH patients.

IReNA: integrated regulatory network analysis of single-cell transcriptomes and chromatin accessibility profiles

“…It has been reported that one of such factors Gata4 could activate heart regeneration in zebrafish and mice [16,17]. In regulatory networks of NASH, we identified Fos and Klf6, which regulate TH17/Treg cells in NASH patients and are up-regulated in the context of steatohepatitis, respectively [18,19].…”

“…When both scRNA-seq and ATAC-seq data are used, a much higher fraction of known transcription factors is identified by IReNA. For instance, in analysis of NASH samples, we identified Fos and Klf6, which regulate TH17/Treg cells in NASH patients and are up-regulated in the context of steatohepatitis, respectively [25,26].…”

“…It has been reported that one of such factors Gata4 could activate heart regeneration in zebrafish and mice [16,17]. In regulatory networks of NASH, we identified Fos and Klf6 , which regulate TH17/Treg cells in NASH patients and are up-regulated in the context of steatohepatitis, respectively [18,19]. The results indicate that IReNA could be applied to identify key modules and transcription factors that regulate a range of different biological processes, although further functional validation of putative key regulators is required.…”

Update on genetics and epigenetics in metabolic associated fatty liver disease

“… 116 In mice on a high cholesterol diet, miR-125b-5p promoter methylation in liver was increased and its expression was reduced, leading to liver fibrosis via integrin α8 (ITGA8). 117 In addition, other miRNAs such as miR-137-3p, 118 miR-103, 119 miR-21, 120 , 121 miRNA-130b-5p, 122 miRNA-27a, 123 miRNA-29c, 124 miRNA-103, 125 miRNA-146b, 126 miRNA-33, 127 miRNA-7a, 128 and miRNA-451 129 are also associated with fatty liver disease caused by metabolic disorders.…”

Regulatory T cells and their associated factors in hepatocellular carcinoma development and therapy

“…Overexpression of miR-195 can maintain the balance of Th17/Treg to ameliorate NAFLD and liver inflammation. Many miRNAs can regulate Th17/Treg cell balance in NAFLD such as miR-29c via interacting with insulin-like growth factor binding protein 1/IGFBP1)[ 55 ]. In addition, other microRNAs such as miR-155[ 56 , 57 ], miR-423-5p[ 58 ], and miR-1246[ 59 ] play important roles in modulating the balance of Tregs with Th17 cells and their functions in liver disease.…”