Comprehensive circular RNA expression profiles in a mouse model of nonalcoholic steatohepatitis

非酒精性脂肪性肝炎小鼠模型中的综合环状 RNA 表达谱

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作者:Qiang Ou, Yajuan Zhao, Jianhua Zhou, Xiaolin Wu

Abstract

Recent studies have revealed that circular RNAs (circRNAs) are involved in the development of various liver diseases. However, the regulatory role of circRNAs in nonalcoholic steatohepatitis (NASH) has not been fully elucidated. In the present study, the circRNA profiles in a NASH mouse model were investigated, and their functions in NASH were predicted using bioinformatics analysis, with the aim of providing novel clues for delineating the mechanisms of action. A NASH mouse model was established by feeding mice with a methionine and choline‑deficient diet. The liver circRNA profile was screened using a circRNA microarray, and the differentially expressed circRNAs were verified by reverse transcription‑quantitative polymerase chain reaction. Subsequently, circRNA‑microRNA (miRNA) interactions were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological functions of host linear transcripts of circRNA. A total of 450 circRNAs were revealed to be dysregulated, with 298 circRNAs upregulated and 152 circRNAs downregulated in the NASH model mice. circRNA_29981 was identified as a significantly differentially expressed circRNA. The results from the circRNA‑miRNA pathway interaction analysis revealed that circRNA_29981 was a potential regulator of hepatic stellate cell activation. The host linear transcripts were also analyzed, and the top 10 enriched GO entries and KEGG pathways were annotated. These findings suggested that circRNAs may be important regulators of NASH. Taken together, the results of the present study demonstrated that the circRNA profile in NASH may provide potential candidates for future studies aimed at elucidating the pathogenic mechanism(s) involved in the disease.

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