Department of Endocrinology and Metabolic Diseases, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, China.
Department of Emergency, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, China.
J Transl Med. 2020 Dec 11;18(1):476. doi: 10.1186/s12967-020-02637-w.
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.
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).
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.
Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.
非酒精性脂肪性肝病（NAFLD）的主要特征是肝内胆固醇积聚。环状 RNA（circRNA）是一种非编码 RNA，参与许多肝脏疾病的进展。然而，以前没有关于 NAFLD 中 circRNA 表达谱的研究。
通过提供高脂肪饮食（HFD）32 周来构建 NAFLD 小鼠模型。使用高通量 RNA 测序方法和生物信息学方法测定正常小鼠和 NAFLD 小鼠的 circRNA 表达谱，并用 Sanger 测序和 qRT-PCR 验证差异表达的 circRNA。还预测了 circRNA-miRNA 网络。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）注释 circRNA 的生物学功能。
免疫组织化学和血清学检测结果表明成功构建了 NAFLD 小鼠模型。总共观察到 93 个失调的 circRNA，包括 57 个上调的 circRNA 和 36 个下调的 circRNA，在 NAFLD 组中。circRNA-miRNA 网络揭示了 circRNA 与其在 NAFLD 中潜在 miRNA 靶标的复杂相互作用。circRNA 组织特异性表达的特征也通过 GO 和 KEGG 进行了注释。DDHA1 和 VAV3 基因都被发现与 NAFLD 的发展有关。
总之，这项研究表明了 NAFLD 中 circRNA 的表达谱和特征，这可能为 NAFLD 的发病机制提供潜在的生物学标志物。
