Integrated Analysis of Hepatic miRNA and mRNA Expression Profiles in the Spontaneous Reversal Process of Liver Fibrosis.

Yang Tai,Huan Tong,Chong Zhao,Chengwei Tang,Yang Xiao,Tian Lan,Jinhang Gao,Rui Liu,Linhao Zhang

doi:10.3389/fgene.2021.706341

Abstract

Liver fibrosis results from the imbalance between extracellular matrix (ECM) production and degradation, which is a common pathological consequence of various chronic liver diseases. Although many miRNAs have been reported in liver fibrosis progression, miRNA-mRNA interactions in its reversal process remain to be elucidated. In the current study, we performed an integrated analysis of miRNA and mRNA expression profiles in the mouse model with the spontaneous reversal potency of liver fibrosis. A total of 102 miRNA and 2,845 mRNAs showed significant differential expression in reversal mice compared to fibrotic mice. Moreover, 3,769 putative negatively correlated miRNA-mRNA pairs were revealed to be potentially implicated in the biological function regulation of small molecule metabolism and ECM organization. By integrating miRNA-mRNA regulatory networks, mmu-miR-1843a-5p, mmu-miR-193a-5p, mmu-miR-194-2-3p, and mmu-miR-30c-2-3p were identified as lysyl oxidases-specific miRNAs that were correlated with fibrosis reversal. Our results provided potential candidate targets for the treatment of liver fibrosis.

Highlights

Liver fibrosis, characterized by the excessive deposition of extracellular matrix (ECM), is a common pathological consequence of various chronic liver diseases, including viral hepatitis, alcoholic and metabolic associated liver diseases (Tsochatzis et al, 2014)
MiRNAs are a class of evolutionarily conserved small (∼23 nucleotides in length), singlestranded non-coding RNA generated from the endogenous transcripts following a series of miRNA-mRNA Regulate Fibrosis Reversal cleavages and modifications (Bartel, 2009)
According to the screening criteria of false discovery rate (FDR) < 0.05 and |fold change| ≥ 2, 206 miRNAs were differentially expressed in the TAA group compared with the control group, among which 102 Differentially expressed miRNAs (DEMs) were reversed in the recovery group (Supplementary Table 2)

Summary

Introduction

Liver fibrosis, characterized by the excessive deposition of extracellular matrix (ECM), is a common pathological consequence of various chronic liver diseases, including viral hepatitis, alcoholic and metabolic associated liver diseases (Tsochatzis et al, 2014). MiRNAs are a class of evolutionarily conserved small (∼23 nucleotides in length), singlestranded non-coding RNA generated from the endogenous transcripts following a series of miRNA-mRNA Regulate Fibrosis Reversal cleavages and modifications (Bartel, 2009). A competitive endogenous RNA hypothesis has been proposed that long non-coding RNAs and circular RNAs may serve as “miRNA sponges” by preferentially occupying the miRNA response elements to regulate mRNAs expression (Thomson and Dinger, 2016), highlighting the central position of miRNAs in cellular function. Accumulated evidence has demonstrated that the dysregulated miRNAs play a crucial role in the development of liver fibrosis by interfering with genes expression and downstream signaling pathways (Wang et al, 2021). Little is known about miRNAs expression profile and their potential functions in the spontaneous reversal of liver fibrosis

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Results

Conclusion