Differential DNA methylation landscape of miRNAs genes in mice liver fibrosis

Abstract

Abstract Background The patients with chronic liver disease were found nearly all to have liver fibrosis, which is characteristic by excess accumulation of extracellular matrix (ECM) proteins. ECM accumulation can destroy normal liver function and architecture except protect from infection and injury. miRNA own regulation was involved in DNA methylation change. The purpose of this study is to detect DNA methylation landscape of miRNAs genes in mice liver fibrosis tissues. Methods 10–12 weeks male mice were injected CCl4 from abdominal cavity to induced liver fibrosis. 850K BeadChips were used to examine DNA methylation change in whole genome. The methylation change of 16 CpG dinucleotides located in promoter regions of 4 miRNA genes were detected by bisulfite sequencing polymerase chain reaction (BSP) to verify chip data accuracy, and these 4 miRNA genes’ expressions were detected by RT-qPCR methods. Results There are 769 differential methylation sites (DMS) in total between fibrotic liver tissue and normal mice liver tissue, which were related with 148 different miRNA genes. Chips array data were confirmed by bisulfite sequencing polymerase chain reaction (R = 0.953; P < 0.01). GO analysis of the target genes of 2 miRNA revealed that protein binding, cytoplasm and chromatin binding activity were commonly enriched; KEGG pathway enrichment analysis displayed TGF-beta signaling pathways were commonly enriched. Conclusion The DNA of 148 miRNA genes was found to have methylation change in liver fibrosis tissue. These discoveries in miRNA genes are beneficial for future miRNA function research in liver fibrosis.