Abstract
BackgroundNonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously.MethodsA NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).ResultsThe results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development.ConclusionsTaken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation
The construction of the NAFLD mouse model NAFLD mouse model was successfully constructed after 32 weeks high-fat diet (HFD), as evidenced by significant fluctuations
Expression profile of Circular RNA (circRNA) in NAFLD mice To identify the differentially expressed circRNAs between the NAFLD group and control group, circRNA sequencing was conducted in each group
Summary
Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. No recent studies on circRNA expression profiles in NAFLD have been reported previously. The circRNAs expression profiles have been reported to mediate neurological diseases, diabetes and lung metastasis. A previous study conducted by Qu et al [10], have suggested a small number of dysregulated circRNAs in the NASH mice fed with methionine/choline deficient diet, and constructed a complex circRNA-miRNA pathway interaction. At this stage, not much information on the circRNAs expression profiles in hepatic tissues of NAFLD have been reported
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