Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data
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Journal of Translational Medicine Open Access
RESEARCH
Circular RNA expression profiles and features in NAFLD mice: a study using RNA‑seq data Xinlu Yuan1, Jianjun Diao2, Anqing Du3, Song Wen1, Ligang Zhou1*† and Yangbin Pan4*†
Abstract Background: Nonalcoholic 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. Methods: A 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). Results: The 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. Conclusions: Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD. Keywords: Nonalcoholic fatty liver disease; circular RNA, Expression profile, Tissue specificity, Regulatory network Background Nonalcoholic fatty liver disease (NAFLD) represents a common chronic liver disease in many developing and developed countries [1]. The prevalence of NAFLD is 20–40% in adult, while approximately 70–80% of occurrence in diabetic and obesity patients. NAFLD *Correspondence: [email protected]; [email protected] † Ligang Zhou and Yangbin Pan contributed equally to this study 1 Department of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai 201399, China 4 Department of Nephrology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai 201399, China Full list of author information is available at the end of the article
encompasses a series of clinical manifestations, such as simple hepatic steatosis and nonalcoholic steatohepatitis (NASH). NASH, an important stage in NAFLD, can even develop to fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [2]. Recently, the occurrence of NAFLD has increased
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