Cao Ziyi, Guan Li, Yu RunZhi, Chen Jie
Department of Gastroenterology, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
Front Genet. 2022 Jun 30;13:931928. doi: 10.3389/fgene.2022.931928. eCollection 2022.
Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease with complex pathogenesis, which brings economic burden to the society, and there is still no effective therapy. Impaired autophagy has been implicated in the development of NAFLD. Long noncoding RNAs (lncRNAs) are also reported to play a role in the pathogenesis of NAFLD. However, the role of autophagy-related lncRNAs in NAFLD disease has not been elucidated. Here, we mined GSE135251, GSE160016, GSE130970 and GSE185062 datasets from the Gene Expression Omnibus database (GEO) and obtained the human autophagy-related gene list from the Human Autophagy Database (HADb) for in-depth bioinformatic analysis. Following differential expression analysis and intersection of the datasets, Pearson correlation analysis was performed on DElncRNAs and autophagy-related DEmRNAs to obtain autophagy-related lncRNAs, and then Starbase3.0 and TargetScan7.2 were used to construct competing endogenous RNAs (ceRNA) regulatory networks. We constructed four lncRNA-dominated ceRNA regulatory networks (PSMG3-AS1, MIRLET7BHG, RP11-136K7.2, LINC00925), and visualized with Cytoscape. Then we performed co-expression analysis of the ceRNA networks and autophagy-related genes, and functionally annotated them with Metascape. Finally, we performed receiver operating characteristic curve (ROC) analysis on lncRNAs and mRNAs within the ceRNA networks. Conclusively, our project is the first to study autophagy-related lncRNAs in NAFLD and finally mined four autophagy-related lncRNAs (PSMG3-AS1, MIRLET7BHG, RP11-136K7.2, LINC00925). We suggested that the four autophagy-related lncRNAs may be closely associated with the occurrence and development of NAFLD through the corresponding ceRNA regulatory networks. This research brings new horizons to the study of NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种发病机制复杂的常见慢性疾病，给社会带来了经济负担，且目前仍无有效的治疗方法。自噬受损与NAFLD的发生发展有关。据报道，长链非编码RNA（lncRNAs）在NAFLD的发病机制中也发挥作用。然而，自噬相关lncRNAs在NAFLD疾病中的作用尚未阐明。在此，我们从基因表达综合数据库（GEO）中挖掘了GSE135251、GSE160016、GSE130970和GSE185062数据集，并从人类自噬数据库（HADb）中获取人类自噬相关基因列表，以进行深入的生物信息学分析。在对数据集进行差异表达分析和交集分析之后，对差异表达的lncRNAs（DElncRNAs）和自噬相关的差异表达信使RNA（DEmRNAs）进行Pearson相关性分析，以获得自噬相关lncRNAs，然后使用Starbase3.0和TargetScan7.2构建竞争性内源RNA（ceRNA）调控网络。我们构建了四个以lncRNA为主导的ceRNA调控网络（PSMG3-AS1、MIRLET7BHG、RP11-136K7.2、LINC00925），并用Cytoscape进行可视化。然后我们对ceRNA网络和自噬相关基因进行共表达分析，并用Metascape对它们进行功能注释。最后，我们对ceRNA网络中的lncRNAs和mRNAs进行受试者工作特征曲线（ROC）分析。总之，我们的项目首次在NAFLD中研究自噬相关lncRNAs，最终挖掘出四个自噬相关lncRNAs（PSMG3-AS1、MIRLET7BHG、RP11-136K7.2、LINC00925）。我们认为，这四个自噬相关lncRNAs可能通过相应的ceRNA调控网络与NAFLD的发生发展密切相关。本研究为NAFLD的研究带来了新的视野。
