Department of Infectious Disease, The Eighth People's Hospital of Shanghai, Shanghai 200235, P.R. China.
Department of Pathology, The Eighth People's Hospital of Shanghai, Shanghai 200235, P.R. China.
Mol Med Rep. 2019 Apr;19(4):2636-2648. doi: 10.3892/mmr.2019.9935. Epub 2019 Feb 5.
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.
最近的研究表明，环状 RNA（circRNA）参与了各种肝脏疾病的发展。然而，circRNA 在非酒精性脂肪性肝炎（NASH）中的调控作用尚未完全阐明。在本研究中，研究人员调查了 NASH 小鼠模型中的 circRNA 谱，并通过生物信息学分析预测了它们在 NASH 中的功能，旨在为阐明作用机制提供新的线索。通过用蛋氨酸和胆碱缺乏饮食喂养小鼠来建立 NASH 小鼠模型。使用 circRNA 微阵列筛选肝脏 circRNA 谱，并通过逆转录定量聚合酶链反应验证差异表达的 circRNA。随后，预测 circRNA-微小 RNA（miRNA）相互作用。对 circRNA 宿主线性转录本的生物学功能进行注释，进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。结果显示，有 450 个 circRNA 被发现失调，其中 298 个 circRNA 在 NASH 模型小鼠中上调，152 个 circRNA 下调。circRNA_29981 被鉴定为差异显著表达的 circRNA。circRNA- miRNA 通路相互作用分析的结果表明，circRNA_29981 是肝星状细胞激活的潜在调节因子。还对 circRNA 宿主线性转录本进行了分析，并注释了前 10 个富集的 GO 条目和 KEGG 通路。这些发现表明 circRNA 可能是 NASH 的重要调节因子。综上所述，本研究的结果表明，NASH 中的 circRNA 谱可能为未来阐明疾病相关致病机制的研究提供潜在的候选物。
